The Scientific World Journal: Developmental Biology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Echocardiographic Assessment of Embryonic and Fetal Mouse Heart Development: A Focus on Haemodynamics and Morphology Sun, 23 Feb 2014 00:00:00 +0000 Background. Heart development is a complex process, and abnormal development may result in congenital heart disease (CHD). Currently, studies on animal models mainly focus on cardiac morphology and the availability of hemodynamic data, especially of the right heart half, is limited. Here we aimed to assess the morphological and hemodynamic parameters of normal developing mouse embryos/fetuses by using a high-frequency ultrasound system. Methods. A timed breeding program was initiated with a WT mouse line (Swiss/129Sv background). All recordings were performed transabdominally, in isoflurane sedated pregnant mice, in hearts of sequential developmental stages: 12.5, 14.5, and 17.5 days after conception (). Results. Along development the heart rate increased significantly from 125 ± 9.5 to 219 ± 8.3 beats per minute. Reliable flow measurements could be performed across the developing mitral and tricuspid valves and outflow tract. M-mode measurements could be obtained of all cardiac compartments. An overall increase of cardiac systolic and diastolic function with embryonic/fetal development was observed. Conclusion. High-frequency echocardiography is a promising and useful imaging modality for structural and hemodynamic analysis of embryonic/fetal mouse hearts. Nathan D. Hahurij, Emmeline E. Calkoen, Monique R. M. Jongbloed, Arno A. W. Roest, Adriana C. Gittenberger-de Groot, Robert E. Poelmann, Marco C. De Ruiter, Conny J. van Munsteren, Paul Steendijk, and Nico A. Blom Copyright © 2014 Nathan D. Hahurij et al. All rights reserved. Functional Characterization of Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) N- and C-Terminal Domains during Xenopus laevis Development Thu, 30 Jan 2014 08:20:39 +0000 Extracellular matrix (ECM) remodeling is essential for facilitating developmental processes. ECM remodeling, accomplished by matrix metalloproteinases (MMPs), is regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs). While the TIMP N-terminal domain is involved in inhibition of MMP activity, the C-terminal domain exhibits cell-signaling activity, which is TIMP and cell type dependent. We have previously examined the distinct roles of the Xenopus laevis TIMP-2 and -3 C-terminal domains during development and here examined the unique roles of TIMP-1 N- and C-terminal domains in early X. laevis embryos. mRNA microinjection was used to overexpress full-length TIMP-1 or its individual N- or C-terminal domains in embryos. Full-length and C-terminal TIMP-1 resulted in increased lethality compared to N-terminal TIMP-1. Overexpression of C-terminal TIMP-1 resulted in significant decreases in mRNA levels of proteolytic genes including TIMP-2, RECK, MMP-2, and MMP-9, corresponding to decreases in MMP-2 and -9 protein levels, as well as decreased MMP-2 and MMP-9 activities. These trends were not observed with the N-terminus. Our research suggests that the individual domains of TIMP-1 are capable of playing distinct roles in regulating the ECM proteolytic network during development and that the unique functions of these domains are moderated in the endogenous full-length TIMP-1 molecule. M. A. Nieuwesteeg, J. A. Willson, M. Cepeda, M. A. Fox, and S. Damjanovski Copyright © 2014 M. A. Nieuwesteeg et al. All rights reserved. Derivation and Characterization of a ES-Like Cell Line from Indian Catfish Heteropneustes fossilis Blastulas Mon, 20 Jan 2014 13:03:26 +0000 A cell line designated as HFB-ES was established from blastula stage embryos of H. fossilis (Singhi). The embryonic cells were harvested and maintained in Leibovitz’s medium supplemented with 15% fetal bovine serum. The cell line had been subcultured for more than 90 passages in a period of 24 months. HFB-ES cells were able to grow at temperatures between 25 and 35°C with an optimum temperature of 28°C. The growth rate of HFB-ES was proportional to FBS concentration, with optimum growth seen at 15% FBS concentration. The originality of the cell line was confirmed by sequencing of cytochrome oxidase c subunit I (COI), cytochrome b gene, and microsatellite DNA profile. Results of chromosome complements of HFB showed normal karyo-morphology with 56 (2) diploid number of chromosomes after 40 passages which indicated that the developed cell line is chromosomally stable. The pluripotency of HFB was demonstrated by alkaline phosphatase activity and Oct-4 gene expression. Expression of GFP reporter gene was successful in HFB-ES. These results indicated that HFB-ES could be utilized for future gene expression studies. Anindya S. Barman, Kuldeep K. Lal, Gaurav Rathore, Vindhya Mohindra, Rajeev K. Singh, Akankaha Singh, Praveen Khare, and Bechan Lal Copyright © 2014 Anindya S. Barman et al. All rights reserved. Lens Extrusion from Laminin Alpha 1 Mutant Zebrafish Wed, 15 Jan 2014 15:36:19 +0000 We report analysis of the ocular lens phenotype of the recessive, larval lethal zebrafish mutant, lama1a69/a69. Previous work revealed that this mutant has a shortened body axis and eye defects including a defective hyaloid vasculature, focal corneal dysplasia, and loss of the crystalline lens. While these studies highlight the importance of laminin 1 in lens development, a detailed analysis of the lens defects seen in these mutants was not reported. In the present study, we analyze the lenticular anomalies seen in the lama1a69/a69 mutants and show that the lens defects result from the anterior extrusion of lens material from the eye secondary to structural defects in the lens capsule and developing corneal epithelium associated with basement membrane loss. Our analysis provides further insights into the role of the lens capsule and corneal basement membrane in the structural integrity of the developing eye. Mallika Pathania, Elena V. Semina, and Melinda K. Duncan Copyright © 2014 Mallika Pathania et al. All rights reserved. The Relationship between the Morphology and Structure and the Quality of Fruits of Two Pear Cultivars (Pyrus communis L.) during Their Development and Maturation Wed, 13 Nov 2013 18:13:59 +0000 The flavour and nutritional values of pears are appreciated by consumers worldwide, who, however, demand specific fruit quality, that is, attractive appearance, firmness and flavour, and health safety as well as long-term shelf life and storability. Pear cultivars differ in terms of the above-mentioned traits; therefore, we undertook investigations to demonstrate the differences in structure of fruits of two pear cultivars that determine fruit quality in its broadest sense. The micromorphology, anatomy, and ultrastructure of “Clapp’s Favourite” and “Conference” fruits in the fruit set stage and in the harvest maturity stage were investigated under light microscope and scanning and transmission electron microscopes. The fruits of “Clapp’s Favourite” and “Conference” in the fruit set stage exhibited distinct differences in the values of anatomical parameters only. Substantial differences in fruit structure were observed in the harvest maturity stage. The analyses indicate that firmness and durability of pear fruits are largely influenced by the presence of russeting, the proportion of closed lenticels and number of stone cells, and the content of starch grains and tannin compounds. The thickness of the cuticle and presence of epicuticular waxes as well as the number of lenticels and the number and depth of microcracks play a minor role. Agata Konarska Copyright © 2013 Agata Konarska. All rights reserved. Islet-1 Immunoreactivity in the Developing Retina of Xenopus laevis Mon, 11 Nov 2013 09:08:27 +0000 The LIM-homeodomain transcription factor Islet1 (Isl1) has been widely used as a marker of neuronal differentiation in the developing visual system of different classes of vertebrates, including mammals, birds, reptiles, and fish. In the present study, we analyzed the spatial and temporal distribution of Isl1-immunoreactive cells during Xenopus laevis retinal development and its relation to the formation of the retinal layers, and in combination with different markers of cell differentiation. The earliest Isl1 expression appeared at St29-30 in the cell nuclei of sparse differentiating neuroblasts located in the vitreal surface of the undifferentiated retina. At St35-36, abundant Isl1-positive cells accumulated at the vitreal surface of the neuroepithelium. As development proceeded and through the postmetamorphic juveniles, Isl1 expression was identified in subpopulations of ganglion cells and in subsets of amacrine, bipolar, and horizontal cells. These data together suggest a possible role for Isl1 in the early differentiation and maintenance of different retinal cell types, and Isl1 can serve as a specific molecular marker for the study of retinal cell specification in X. laevis. Guadalupe Álvarez-Hernán, Ruth Bejarano-Escobar, Ruth Morona, Agustín González, Gervasio Martín-Partido, and Javier Francisco-Morcillo Copyright © 2013 Guadalupe Álvarez-Hernán et al. All rights reserved. Early Neural Cell Death Is an Extensive, Dynamic Process in the Embryonic Chick and Mouse Retina Tue, 09 Apr 2013 15:11:23 +0000 Orchestrated proliferation, differentiation, and cell death contribute to the generation of the complex cytoarchitecture of the central nervous system, including that of the neuroretina. However, few studies have comprehensively compared the spatiotemporal patterns of these 3 processes, or their relative magnitudes. We performed a parallel study in embryonic chick and mouse retinas, focusing on the period during which the first neurons, the retinal ganglion cells (RGCs), are generated. The combination of in vivo BrdU incorporation, immunolabeling of retinal whole mounts for BrdU and for the neuronal markers Islet1/2 and βIII-tubulin, and TUNEL allowed for precise cell scoring and determination the spatiotemporal patterns of cell proliferation, differentiation, and death. As predicted, proliferation preceded differentiation. Cell death and differentiation overlapped to a considerable extent, although the magnitude of cell death exceeded that of neuronal differentiation. Precise quantification of the population of recently born RGCs, identified by BrdU and βIII-tubulin double labeling, combined with cell death inhibition using a pan-caspase inhibitor, revealed that apoptosis decreased this population by half shortly after birth. Taken together, our findings provide important insight into the relevance of cell death in neurogenesis. Teresa Chavarría, Jimena Baleriola, Raquel Mayordomo, Flora de Pablo, and Enrique J. de la Rosa Copyright © 2013 Teresa Chavarría et al. All rights reserved. Embryonic, Larval, and Early Juvenile Development of the Tropical Sea Urchin, Salmacis sphaeroides (Echinodermata: Echinoidea) Thu, 27 Sep 2012 10:05:38 +0000 Salmacis sphaeroides (Linnaeus, 1758) is one of the regular echinoids, occuring in the warm Indo-West Pacific, including Johor Straits, between Malaysia and Singapore. In order to investigate the developmental basis of morphological changes in embryos and larvae, we documented the ontogeny of S. sphaeroides in laboratory condition. Gametes were obtained from adult individuals by 0.5 M KCl injection into the coelomic cavity. Fertilization rate at limited sperm concentration ( dilution) was % and the resulting embryos were reared at 24°C. First cleavage (2-cell), 4-cell, 8-cell, 16-cell, 32-cell, and multicell (Morulla) stages were achieved 01.12, 02.03, 02.28, 02.51, 03.12, and 03.32 h postfertilization. Ciliated blastulae with a mean length of  μm hatched 08.45 h after sperm entry. The gastrulae formed 16.15 h postfertilization and the archenteron elongated constantly while ectodermal red-pigmented cells migrated synchronously to the apical plate. Pluteus larva started to feed unicellular algae in 2 d, grew continuously, and finally attained metamorphic competence in 35 d after fertilization. Metamorphosis took approximately 1 h 30 min from attachment to the complete resorption of larval tissues and the development of complete juvenile structure with adult spines, extended tubefeet and well-developed pedicellaria, the whole event of which usually took place within 1 d postsettlement. This study represents the first successful investigation on embryonic, larval, and early juvenile development of S. sphaeroides. The findings would greatly be helpful towards the understanding of ontogeny and life-history strategies, which will facilitate us to develop the breeding, seed production, and culture techniques of sea urchins in captive condition. M. Aminur Rahman, Fatimah Md. Yusoff, A. Arshad, Mariana Nor Shamsudin, and S. M. N. Amin Copyright © 2012 M. Aminur Rahman et al. All rights reserved. Selection of the In Vitro Culture Media Influences mRNA Expression of Hedgehog Genes, Il-6, and Important Genes regarding Reactive Oxygen Species in Single Murine Preimplantation Embryos Tue, 31 Jul 2012 14:07:04 +0000 Background. The aim of this paper was to determine the influence of different in vitro culture media on mRNA expression of Hedgehog genes, il-6, and important genes regarding reactive oxygen species in single mouse embryos. Methods. Reverse transcription of single embryos either cultured in vitro from day 0.5 until 3.5 (COOK’s Cleavage medium or Vitrolife’s G-1 PLUS medium) or in vivo until day 3.5 post coitum. PCR was carried out for β-actin followed by nested-PCR for shh, ihh, il-6, nox, gpx4, gpx1, and prdx2. Results. The number of murine blastocysts cultured in COOK medium which expressed il-6, gpx4, gpx1, and prdx2 mRNA differed significantly compared to the in vivo group. Except for nox, the mRNA profile of the Vitrolife media group embryos varied significantly from the in vivo ones regarding the number of blastocysts expressing the mRNA of shh, ihh, il-6, gpx4, gpx1 and prdx2. Conclusions. The present study shows that different in vitro culture media lead to different mRNA expression profiles during early development. Even the newly developed in vitro culture media are not able to mimic the female reproductive tract. The question of long-term consequences for children due to assisted reproduction techniques needs to be addressed in larger studies. N. Pfeifer, D. M. Baston-Büst, J. Hirchenhain, U. Friebe-Hoffmann, D. T. Rein, J. S. Krüssel, and A. P. Hess Copyright © 2012 N. Pfeifer et al. All rights reserved. Development of Communication Behaviour: Receiver Ontogeny in Túngara Frogs and a Prospectus for a Behavioural Evolutionary Development Wed, 02 May 2012 11:24:54 +0000 Most studies addressing the development of animal communication have focused on signal production rather than receiver decoding, and similar emphasis has been given to learning over nonlearning. But receivers are an integral part of a communication network, and nonlearned mechanisms appear to be more ubiquitous than learned ones in the communication systems of most animals. Here we review the results of recent experiments and outline future directions for integrative studies on the development of a primarily nonlearned behaviour—recognition of communication signals during ontogeny in a tropical frog. The results suggest that antecedents to adult behaviours might be a common feature of developing organisms. Given the essential role that acoustic communication serves in reproduction for many organisms and that receivers can exert strong influence on the evolution of signals, understanding the evolutionary developmental basis of mate recognition will provide new insights into the evolution of communication systems. Alexander T. Baugh, Kim L. Hoke, and Michael J. Ryan Copyright © 2012 Alexander T. Baugh et al. All rights reserved. Embryonic Regulation of the Mouse Hematopoietic Niche Tue, 18 Oct 2011 00:00:00 +0000 Hematopoietic stem cells (HSCs) can differentiate into several types of hematopoietic cells (HCs) (such as erythrocytes, megakaryocytes, lymphocytes, neutrophils, or macrophages) and also undergo self-renewal to sustain hematopoiesis throughout an organism's lifetime. HSCs are currently used clinically as transplantation therapy in regenerative medicine and are typically obtained from healthy donors or cord blood. However, problems remain in HSC transplantation, such as shortage of cells, donor risks, rejection, and graft-versus-host disease (GVHD). Thus, increased understanding of HSC regulation should enable us to improve HSC therapy and develop novel regenerative medicine techniques. HSC regulation is governed by two types of activity: intrinsic regulation, programmed primarily by cell autonomous gene expression, and extrinsic factors, which originate from so-called “niche cells” surrounding HSCs. Here, we focus on the latter and discuss HSC regulation with special emphasis on the role played by niche cells. Daisuke Sugiyama, Tomoko Inoue-Yokoo, Stuart T. Fraser, Kasem Kulkeaw, Chiyo Mizuochi, and Yuka Horio Copyright © 2011 Daisuke Sugiyama et al. All rights reserved. Lipoxins: A Novel Regulator in Embryo Implantation Mon, 01 Jan 1900 00:00:00 +0000 Embryo implantation is essential for mammalian pregnancy, which involves intricate cross-talk between the blastocyst and the maternal endometrium. Recent advances have identified various molecules crucial to implantation and endometrial receptivity, including leukemia inhibitory factor, calcitonin, and homeobox A10. There is a close relationship between implantation and inflammation. Lipoxins, important in the resolution of inflammation, may be a potential regulator in implantation. Here we discuss the hypothesis that lipoxins may work as a novel regulator in embryo implantation and the possible molecular mechanisms. Jing Xiong, Pan Zeng, and Duyun Ye Copyright © 2011 Xiong Jing et al. All rights reserved. Zebrafish Fins as a Model System for Skeletal Human Studies Mon, 01 Jan 1900 00:00:00 +0000 Recent studies on the morphogenesis of the fins of Danio rerio (zebrafish) during development and regeneration suggest that a number of inductive signals involved in the process are similar to some of those that affect bone and cartilage differentiation in mammals and humans. Akimenko et al. (2002) has shown that bone morphogenetic protein-2b (BMP2b) is involved in the induction of dermal bone differentiation during fin regeneration. Many other groups have also shown that molecules from the transforming growth factor-beta superfamily (TGFβ), including BMP2, are effective in promoting chondrogenesis and osteogenesis in vivo in higher vertebrates, including humans. In the present study, we review the state of the art of this topic by a comparative analysis of skeletal tissue development, regeneration and renewal processes in tetrapods, and fin regeneration in fishes. A general conclusion of this study states that lepidotrichia is a special skeletal tissue different to cartilage, bone, enamel, or dentine in fishes, according to its extracellular matrix (ECM) composition. However, the empirical analysis of inducing signals of skeletal tissues in fishes and tetrapods suggests that lepidotrichia is different to any responding features with main skeletal tissues. A number of new inductive molecules are arising from fin development and regeneration studies that might establish an empirical basis for further molecular approaches to mammal skeletal tissues differentiation. Despite the tissue dissimilarity, this empirical evidence might finally lead to clinical applications to skeletal disorders in humans. Manuel Marí-Beffa, Jesús A. Santamaría, Carmen Murciano, Leonor Santos-Ruiz, José A. Andrades, Enrique Guerado, and José Becerra Copyright © 2007 Manuel Marí-Beffa et al. All rights reserved. Impact of Mitochondrial Dynamics on Organismic Aging Mon, 01 Jan 1900 00:00:00 +0000 Christian Q. Scheckhuber Copyright © 2009 Christian Q. Scheckhuber. All rights reserved. The Role of Xchk1 in The Inhibition of Apoptosis Mon, 01 Jan 1900 00:00:00 +0000 Ayesha D. Carter and Jill C. Sible Copyright © 2001 Ayesha D. Carter and Jill C. Sible. All rights reserved. Stress-Induced Premature Senescence or Stress-Induced Senescence-Like Phenotype: One In Vivo Reality, Two Possible Definitions? Mon, 01 Jan 1900 00:00:00 +0000 No consensus exists so far on the definition of cellular senescence. The narrowest definition of senescence is irreversible growth arrest triggered by telomere shortening counting cell generations (definition 1). Other authors gave an enlarged functional definition encompassing any kind of irreversible arrest of proliferative cell types induced by damaging agents or cell cycle deregulations after overexpression of proto-oncogenes (definition 2). As stress increases, the proportion of cells in “stress-induced premature senescence-like phenotype” according to definition 1 or “stress-induced premature senescence,” according to definition 2, should increase when a culture reaches growth arrest, and the proportion of cells that reached telomere-dependent replicative senescence due to the end-replication problem should decrease. Stress-induced premature senescence-like phenotype and telomere-dependent replicatively senescent cells share basic similarities such as irreversible growth arrest and resistance to apoptosis, which may appear through different pathways. Irreversible growth arrest after exposure to oxidative stress and generation of DNA damage could be as efficient in avoiding immortalisation as “telomere-dependent” replicative senescence. Probabilities are higher that the senescent cells (according to definition 2) appearing in vivo are in stress-induced premature senescence rather than in telomere-dependent replicative senescence. Examples are given suggesting these cells affect in vivo tissue (patho)physiology and aging. Olivier Toussaint, Patrick Dumont, Jose Remacle, Jean-Francois Dierick, Thierry Pascal, Christophe Frippiat, Joao Pedro Magalhaes, Stephanie Zdanov, and Florence Chainiaux Copyright © 2002 Olivier Toussaint et al. All rights reserved. Squeezing an Egg into a Worm: C. elegans Embryonic Morphogenesis Mon, 01 Jan 1900 00:00:00 +0000 We review key morphogenetic events that occur during Caenorhabditis elegans ( embryogenesis. Morphogenesis transforms tissues from one shape into another through cell migrations and shape changes, often utilizing highly conserved actin-based contractile systems. Three major morphogenetic events occur during C. elegans embryogenesis: (1) dorsal intercalation, during which two rows of dorsal epidermal cells intercalate to form a single row; (2) ventral enclosure, where the dorsally located sheet of epidermal cells stretches to the ventral midline, encasing the embryo within a single epithelial sheet; and (3) elongation, during which actin-mediated contractions within the epithelial sheet lengthens the embryo. Here, we describe the known molecular players involved in each of these processes. A. J. Piekny and P. E. Mains Copyright © 2003 A. J. Piekny and P. E. Mains. All rights reserved. Time-Space Translation: A Developmental Principle Mon, 01 Jan 1900 00:00:00 +0000 We review a recently discovered developmental mechanism. Anterior-posterior positional information for the vertebrate trunk is generated by sequential interactions between a timer in the early nonorganizer mesoderm (NOM) and the Spemann organizer (SO). The timer is characterized by temporally collinear activation of a series of Hox genes in the early ventral and lateral mesoderm (i.e., the NOM) of the Xenopus gastrula. This early Hox gene expression is transient, unless it is stabilized by signals from the SO. The NOM and the SO undergo timed interactions due to morphogenetic movements during gastrulation, which lead to the formation of an anterior-posterior axial pattern and stable Hox gene expression. When separated from each other, neither the NOM nor the SO is able to induce anterior-posterior pattern formation of the trunk. We present a model describing that the NOM acquires transiently stable hox codes and spatial collinearity, and that morphogenetic movements then continually bring new cells from the NOM within the range of SO signals that cause transfer of the mesodermal pattern to a stable pattern in neurectoderm and, thereby, create patterned axial structures. In doing so, the age of the NOM, but not the age of the SO, defines positional values along the anterior-posterior axis. We postulate that the temporal information from the NOM is linked to mesodermal Hox expression. The role of the SO for trunk patterning turns out to be the induction of neural tissue as prerequisite for neural hox patterning. Apparently, development of a stable anterior-posterior pattern requires neural hox patterning. We believe that this mechanism represents a developmental principle. A. J. Durston, H. J. Jansen, and S. A. Wacker Copyright © 2010 A. J. Durston et al. All rights reserved. Human Development VII: A Spiral Fractal Model of Fine Structure of Physical Energy Could Explain Central Aspects of Biological Information, Biological Organization and Biological Creativity Mon, 01 Jan 1900 00:00:00 +0000 In this paper we have made a draft of a physical fractal essence of the universe, a sketch of a new cosmology, which we believe to lay at the root of our new holistic biological paradigm. We present the fractal roomy spiraled structures and the energy-rich dancing “infinite strings” or lines of the universe that our hypothesis is based upon. The geometric language of this cosmology is symbolic and both pre-mathematical and pre-philosophical. The symbols are both text and figures, and using these we step by step explain the new model that at least to some extent is able to explain the complex informational system behind morphogenesis, ontogenesis, regeneration and healing. We suggest that it is from this highly dynamic spiraled structure that organization of cells, organs, and the wholeness of the human being including consciousness emerge. The model of ““dancing fractal spirals” carries many similarities to premodern cultures descriptions of the energy of the life and universe. Examples are the Native American shamanistic descriptions of their perception of energy and the old Indian Yogis descriptions of the life-energy within the body and outside. Similar ideas of energy and matter are found in the modern superstring theories. The model of the informational system of the organism gives new meaning to Bateson’s definition of information: “A difference that makes a difference”, and indicates how information-directed self-organization can exist on high structural levels in living organisms, giving birth to their subjectivity and consciousness. Søren Ventegodt, Tyge Dahl Hermansen, Trine Flensborg-Madsen, Erik Rald, Maj Lyck Nielsen, and Joav Merrick Copyright © 2006 Søren Ventegodt et al. All rights reserved. Publication of a Special Issue: Limb and Fin Regeneration Mon, 01 Jan 1900 00:00:00 +0000 Claire Redhead Copyright © 2007 TheScientificWorldJOURNAL All rights reserved. Early Head Specification in Xenopus laevis Mon, 01 Jan 1900 00:00:00 +0000 The head represents the most dorsal and anterior extent of the body axis. In Xenopus, the progressive determination of the head is an extremely complex process involving the activation and localized antagonism of a number of interdependent intracellular signaling pathways including the Wingless/Int-1 (Wnt), bone morphogenetic protein (BMP), and nodal-related pathways. The sequence of events that specify the head are: dorsal-ventral polarization and head organizer specification in the blastula; gastrulation; neural induction; and patterning of the anterior-posterior and dorsal-ventral neuraxes. Wnt signaling is required for the specification of the dorsal side initially but is then inhibited within the organizer once it has formed. Similarly, Wnt signaling is required along the length of the neural tube, but must be suppressed at its rostral end for normal brain development. Nodal signaling is also necessary for induction of the mesendoderm, but is subsequently suppressed in its dorsal-anterior extreme to specify head organizer. BMP signaling is required for ventral mesoderm and non-neural ectoderm, and must also be suppressed in the head organizer region and for the differentiation of the ventral midline of the neural tube. Thus, development of the head, and indeed the body plan in general, requires precisely timed and spatially restricted activation and repression of these signaling pathways. Blue B. Lake and Kenneth R. Kao Copyright © 2003 Blue B. Lake and Kenneth R. Kao. All rights reserved. Human development I: Twenty Fundamental Problems of Biology, Medicine, and Neuro-Psychology Related to Biological Information Mon, 01 Jan 1900 00:00:00 +0000 In a new series of papers, we address a number of unsolved problems in biology today. First of all, the unsolved enigma concerning how the differentiation from a single zygote to an adult individual happens has been object for severe research for decades. By uncovering a new holistic biological paradigm that introduces an energetic-informational interpretation of reality as a new way to experience biology, these papers will try to solve the problems connected with the events of biological ontogenesis involving a fractal hierarchy, from a single cell to the function of the human brain. The problems discussed are interpreted within the frames of a universe of roomy fractal structures containing energetic patterns that are able to deliver biological information. We think biological organization is guided by energetic changes on the level of quantum mechanics, interacting with the intention that again guides the energetic conformation of the fractal structures to gain disorders or healthiness. Furthermore, we introduce two new concepts: “metamorphous top down” evolution and “adult human metamorphosis”. The first is a new evolutionary theory involving metamorphosis as a main concept of evolution. The last is tightly linked to the evolutionary principle and explains how human self-recovery is governed. Other subjects of special interest that we shall look deeper into are the immunological self-nonself discrimination, the structure and function of the human brain, the etiology and salutogenesis of mental and somatic diseases, and the structure of the consciousness of a human being. We shall criticize Szentagothai’s model for the modulated structure of the human cerebral cortex and Jerne’s theory of the immunological regulatory anti-idiotypic network. Tyge Dahl Hermansen, Søren Ventegodt, Erik Rald, Birgitte Clausen, Maj Lyck Nielsen, and Joav Merrick Copyright © 2006 Tyge Dahl Hermansen et al. All rights reserved. U.S. Science Politics are Top Headlines in Both Journals Mon, 01 Jan 1900 00:00:00 +0000 Nature and Science open the news week with an introduction to U.S. President Bush’s choice for the nation’s science advisor post as their top subject. Both journals also report in their second slots on the same administration’s difficulties developing national stem cell and cloning policies. Shauna M. Haley Copyright © 2001 Shauna M. Haley. All rights reserved. Human development II: We Need an Integrated Theory for Matter, Life and Consciousness to Understand Life and Healing Mon, 01 Jan 1900 00:00:00 +0000 For almost a decade, we have experimented with supporting the philosophical development of severely ill patients to induce recovery and spontaneous healing. Recently, we have observed a new pattern of extremely rapid, spontaneous healing that apparently can facilitate even the spontaneous remission of cancer and the spontaneous recovery of mental diseases like schizophrenia and borderline schizophrenia. Our working hypothesis is that the accelerated healing is a function of the patient’s brain-mind and body-mind coming closer together due to the development of what we call “deep” cosmology. To understand and describe what happens at a biological level, we have suggested naming the process adult human metamorphosis, a possibility that is opened by the human genome showing full generic equipment for metamorphosis. To understand the mechanistic details in the complicated interaction between consciousness and biology, we need an adequate theory for biological information. In a series of papers, we propose what we call “holistic biology for holistic medicine”. We suggest that a relatively simple model based on interacting wholenesses instead of isolated parts can shed a new light on a number of difficult issues that we need to explain and understand in biology and medicine in order to understand and use metamorphosis in the holistic medical clinic. We aim to give a holistic theoretical interpretation of biological phenomena at large, morphogenesis, evolution, immune system regulation (self-nonself discrimination), brain function, consciousness, and health in particular. We start at the most fundamental problem: what is biological information at the subcellular, cellular, and supracellular levels if we presume that it is the same phenomenon on all levels (using Occam's razor), and how can this be described scientifically? The problems we address are all connected to the information flow in the functioning, living organism: function of the brain and consciousness, the regulations of the immune system and cell growth, the dynamics of health and disease. We suggest that life utilizes an unseen fine structure of the physical energy of the universe at a subparticular or quantum level to give information-directed self-organization; we give a first sketch of a possible fractal structure of the energy able to both contain and communicate biological information and carry individual and collective consciousness. Finally, thorough our analysis, we put up a model for adult human metamorphosis. Sören Ventegodt, Tyge Dahl Hermansen, Maj Lyck Nielsen, Birgitte Clausen, and Joav Merrick Copyright © 2006 Sören Ventegodt et al. All rights reserved. Making Headway: The Roles of Hox Genes and Neural Crest Cells in Craniofacial Development Mon, 01 Jan 1900 00:00:00 +0000 Craniofacial development is an extraordinarily complex process requiring the orchestrated integration of multiple specialized tissues such as the surface ectoderm, neural crest, mesoderm, and pharyngeal endoderm in order to generate the central and peripheral nervous systems, axial skeleton, musculature, and connective tissues of the head and face. How do the characteristic facial structures develop in the appropriate locations with their correct shapes and sizes, given the widely divergent patterns of cell movements that occur during head development? The patterning information could depend upon localized interactions between the epithelial and mesenchymal tissues or alternatively, the developmental program for the characteristic facial structures could be intrinsic to each individual tissue precursor. Understanding the mechanisms that control vertebrate head development is an important issue since craniofacial anomalies constitute nearly one third of all human congenital defects. This review discusses recent advances in our understanding of neural crest cell patterning and the dynamic nature of the tissue interactions that are required for normal craniofacial development. Paul A. Trainor Copyright © 2003 Paul A. Trainor. All rights reserved. Induction of Primordial Germ Cells from Pluripotent Epiblast Mon, 01 Jan 1900 00:00:00 +0000 The formation of germ cells during embryogenesis bears the ultimate importance for the continuation of every species. It becomes evident that mechanisms governing germ cell fate specification are not well conserved across the animal kingdom. In most of the invertebrate and nonmammalian vertebrate species, certain maternally derived factors are key to the establishment of germ cell lineage. In contrast, mouse primordial germ cells (PGCs) are induced from the pluripotent epiblast cells before and during gastrulation by the extraembryonic cell-derived signals. The molecular identity for some of these signals has recently been revealed by genetic and epiblast culture experiments. Both bone morphogenetic proteins 4 (Bmp4) and 8b (Bmp8b) are expressed in the extraembryonic ectoderm and are required for PGC formation. Furthermore, BMP4 or BMP8B alone are unable to induce PGCs from cultured epiblasts, while they can in combination, indicating they signal through separate receptor complexes. In addition, Bmp4 homozygous embryos cannot be induced to form PGCs by the synergistic action of BMP4 and BMP8B, suggesting that BMP4 proteins produced by pregastrula embryos are required for epiblast cells to maintain pluripotency. Moreover, Bmp2, a close relative of Bmp4, is expressed in visceral endoderm at the time of PGC specification, and inactivation of Bmp2 results in a reduction in PGC number, revealing a novel function of visceral endoderm in PGC generation in the mouse. Ying Ying, Xiaoxia Qi, and Guang-Quan Zhao Copyright © 2002 Ying Ying et al. All rights reserved. Embryonic Stem Cell Lines of Nonhuman Primates Mon, 01 Jan 1900 00:00:00 +0000 Human embryonic stem (ES) cell lines have opened great potential and expectation for cell therapy and regenerative medicine. Monkey and human ES cell lines, which are very similar to each other, have been established from monkey blastocysts and surplus human blastocysts from fertility clinics.Nonhuman primate ES cell lines provide important research tools for basic and applicative research. Firstly, they provide wider aspects of investigation of the regulative mechanisms of stem cells and cell differentiation among primate species. Secondly, their usage does not need clearance or permission from the regulative rules in many countries that are associated with the ethical aspects of human ES cells, although human and nonhuman embryos and fetuses are very similar to each other. Lastly and most importantly, they are indispensable for animal models of cell therapy to test effectiveness, safety, and immunological reaction of the allogenic transplantation in a setting similar to the treatment of human diseases.So far, ES cell lines have been established from rhesus monkey (Macaca mulatta), common marmoset (Callithrix jacchus), and cynomolgus monkey (Macaca fascicularis), using blastocysts produced naturally or by in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). These cell lines seem to have very similar characteristics. They express alkaline phosphatase activity and stage-specific embryonic antigen (SSEA)-4 and, in most cases, SSEA-3. Their pluripotency was confirmed by the formation of embryoid bodies and differentiation into various cell types in culture and also by the formation of teratomas that contained many types of differentiated tissues including derivatives of three germ layers after transplantation into the severe combined immunodeficiency (SCID) mice. The noneffectiveness of the leukemia inhibitory factor (LIF) signal makes culture of primate and human ES cell lines prone to undergo spontaneous differentiation and thus it is difficult to maintain these stem cell colonies. Also, these ES cells are more susceptible to various stresses, causing difficulty with subculturing using enzymatic treatment and cloning from single cells. However, with various improvements in culture methods, it is now possible to maintain stable colonies of monkey ES cells using a serum-free medium and subculturing with trypsin treatment. Under such conditions, cynomolgus monkey ES cell lines can be maintained in an undifferentiated state with a normal karyotype and pluripotency even after prolonged periods of culture over 1 year. Such progress should facilitate many aspects of stem cell research using both nonhuman primate and human ES cell lines. Norio Nakatsuji and Hirofumi Suemori Copyright © 2002 Norio Nakatsuji and Hirofumi Suemori. All rights reserved. Coupling Planar Cell Polarity Signaling to Morphogenesis Mon, 01 Jan 1900 00:00:00 +0000 Epithelial cells and other groups of cells acquire a polarity orthogonal to their apical–basal axes, referred to as Planar Cell Polarity (PCP). The process by which these cells become polarized requires a signaling pathway using Frizzled as a receptor. Responding cells sense cues from their environment that provide directional information, and they translate this information into cellular asymmetry. Most of what is known about PCP derives from studies in the fruit fly, Drosophila. We review what is known about how cells translate an unknown signal into asymmetric cytoskeletal reorganization. We then discuss how the vertebrate processes of convergent extension and cochlear hair-cell development may relate to Drosophila PCP signaling. Jeffrey D. Axelrod and Helen McNeill Copyright © 2002 Jeffrey D. Axelrod and Helen McNeill. All rights reserved. Founding Editorial: Embryology — An Integrated Approach Mon, 01 Jan 1900 00:00:00 +0000 We introduce the Embryology domain of TheScientificWorld and outline the scope and aims. We argue for an interdisciplinary approach to problems in develop-mental biology. Three areas are identified as being of particular relevance to this domain: evolutionary developmental biology, teratology, and descriptive or experimental embryology. Michael Richardson, Roger Keynes, Paula Mabee, and Lynne Selwood Copyright © 2001 Michael Richardson et al. All rights reserved. Morphogenesis of the Metanephric Kidney Mon, 01 Jan 1900 00:00:00 +0000 The metanephric (permanent) kidney of the mouse is an exceptionally well-studied example of organ development. Its morphogenesis begins on the meeting of two tissues, the epithelial ureteric bud and the metanephrogenic mesenchyme; a series of signalling events between these tissues and their successors organizes the organ as it grows and matures. Many of the signals have been identified at the molecular level. They include GDNF, neurturin, persephin, HGF, BMP-2, BMP-7, FGF-10, activin, and TGFb (all of which control development of the ureteric bud); TGFa, TIMP-2, BMP-4, and BMP7 (all of which control development of the mesenchyme); LIF, FGF-2, TGFb, Wnt-4, sFrp, Notch, and Jagged (all of which control nephron development); and VEGF (which controls vascularization). Many of these signals are arranged in feedback loops, so that cells entering one developmental pathway signal back to ensure that other cells are more likely to enter alternative pathways, and thus keep the relative proportions and positions of different renal tissues in balance. Jamie A. Davies Copyright © 2002 Jamie A. Davies. All rights reserved. Vitamin A Prevents Inner Ear Defects in Mice with Congenital Homeobox Gene Deficiency Mon, 01 Jan 1900 00:00:00 +0000 For the past 75 years, vitamin A and its biologically active metabolites, the retinoids, have been the object of intense study in biology and medicine. A large body of evidence demonstrates that these nutrients are essential for normal development and survival of vertebrate embryos, including mammals[1,2,3,4]. In fact, it has been known since the mid-1930s that vitamin A deficiency during pregnancy results in death of the fetus and congenital abnormalities. Similarly, excess dietary intake of vitamin A can also cause teratogenic responses. Among the main targets of both deficiency and excess retinoid-induced teratogenesis are the heart, limbs, craniofacial structures, central nervous system, and the inner ear. Specific malformations are induced in a stage- and dose-dependent manner. Thus, these studies indicate that precise levels and timing of action of vitamin A metabolites are required for normal patterning of embryonic structures. In addition, the discovery of the nuclear receptors for retinoic acid (RA) and other vitamin A derivatives provided a molecular basis to explain how distinct doses of these compounds elicit cell-specific responses via the direct transcriptional activation of a panel of target genes[5]. Massimo Pasqualetti and Filippo M. Rijli Copyright © 2001 Massimo Pasqualetti and Filippo M. Rijli. All rights reserved. Human development IV: The Living Cell has Information-Directed Self-Organisation Mon, 01 Jan 1900 00:00:00 +0000 In this paper, restricted to describe the ontogenesis of the cell, we discuss the processing of DNA through RNA to proteins and argue that this process is not able to transfer the information necessary to organize the proteins in the cell, but only to transfer the information necessary to form the shape of the proteins. We shortly describe the structure of the information carrying field recruited by the cells that we think is responsible for building the organelles and other cellular structures. We use the cells superior control of its cytoskeleton as an example of how the cell is using an informational field giving the positional information guiding all the local chemical processes behind the cell movement. We describe the information-directed self-organization in cells and argue that this can explain the ontogenesis of the cell. We also suggest the existence of an undiscovered phenomenon behind the information transmitting cell interactions. We conclude that during evolution the cell has developed into an information-guided self-organizing structure. The mystery we want to solve is: what is the mechanical cause and nature of biological information? Søren Ventegodt, Tyge Dahl Hermansen, Trine Flensborg-Madsen, Maj Lyck Nielsen, Birgitte Clausen, and Joav Merrick Copyright © 2006 Søren Ventegodt et al. All rights reserved. Human Development VI: Supracellular Morphogenesis. The Origin of Biological and Cellular Order Mon, 01 Jan 1900 00:00:00 +0000 Uninterrupted morphogenesis shows the informational potentials of biological organisms. Experimentally disturbed morphogenesis shows the compensational dynamics of the biological informational system, which is the rich informational redundancy. In this paper, we use these data to describe morphogenesis in terms of the development of supracellular levels of the organism, and we define complex epigenesis and supracellular differentiation. We review the phenomena of regeneration and induction of Hydra and amphibians, and the higher animal’s informational needs for developing their complex nervous systems. We argue, also building on the NO-GO theorem for ontogenesis as chemistry, that the traditional chemical explanations of high-level informational events in ontogenesis, such as transmutation, regeneration, and induction, are insufficient. We analyze the informational dynamics of three embryonic compensatory reactions to different types of disturbances: (1) transmutations of the imaginal discs of insects, (2) regeneration after removal of embryonic tissue, and (3) embryonic induction, where two tissues that normally are separated experimentally are made to influence each other. We describe morphogenesis as a complex bifurcation, and the resulting morphological levels of the organism as organized in a fractal manner and supported by positional information. We suggest that some kind of real nonchemical phenomenon must be taking form in living organisms as an information-carrying dynamic fractal field, causing morhogenesis and supporting the organism’s morphology through time. We argue that only such a phenomenon that provides information-directed self-organization to the organism is able to explain the observed dynamic distribution of biological information through morphogenesis and the organism's ability to rejuvenate and heal. Søren Ventegodt, Tyge Dahl Hermansen, Trine Flensborg-Madsen, Maj Lyck Nielsen, and Joav Merrick Copyright © 2006 Søren Ventegodt et al. All rights reserved. Postimplantation Whole Embryo Culture Assay for Hamsters: An Alternative to Rat and Mouse Mon, 01 Jan 1900 00:00:00 +0000 Postimplantation whole embryo culture (WEC) assay for rats and mice has been well established and introduced to many laboratories. Recently WEC technique for rabbits has been developed; however, information on culture of other species is very limited. Knowing the usefulness of hamsters in classical embryotoxicology, we reasoned that hamster WEC could be an alternative model for the most frequently used rat and mouse WEC. Previously we have optimized culture conditions for postimplantation hamster embryos. The aim of this study was to test the susceptibility of hamster embryos cultured in vitro to embryotoxic compounds and to compare our results with those reported by others on rat or mouse embryo culture. For that purpose we choose three known embryotoxic compounds—valproic acid, cadmium chloride, and diethylstilbestrol—and tested them using a postimplantation hamster whole embryo culture assay. Hamster embryos were cultured from 7.5 days gestation for 24 h in a medium consisting of 35% hamster serum and 65% synthetic culture medium (Iscove’s or McCoy 5A). At the end of the culture period, the embryos were examined morphologically, measured with the aid of a computer image analysis system, and total protein content was assessed. All three compounds exhibited dose-related embryotoxic and teratogenic effects in hamster embryos. The malformations observed were similar to those reported on rat and mouse embryos. Comparison of the results with data reported by other authors indicates that hamster embryos cultured in vitromight be more susceptible to embryotoxic stimuli than rat and mouse embryos. Bogdan Wlodarczyk, Bogumil Biernacki, Maria Minta, and Jan Zmudzki Copyright © 2001 Bogdan Wlodarczyk et al. All rights reserved.