Neural Conversion and Patterning of Human Pluripotent Stem Cells: A Developmental Perspective

Figure 4

Neural patterning. (a) Rostrocaudal gradients of Nodal, BMP4, RA (retinoic acid), and FGF8 important in rostrocaudal patterning. (b) The interplay between different factors encoding forebrain (PAX6 and OTX2), midbrain (PAX6, OTX2, and EN1/PAX2), and hindbrain (EN1/PAX2, GBX2, and FGF8). The forebrain-midbrain barrier is defined by the mutually exclusive expression of PAX6 (forebrain) and EN1/PAX2 (midbrain), while the midbrain-hindbrain boundary by OTX2 (midbrain) and GBX2 (hindbrain). OTX2 and GBX2 are regulated by FGF8 expression. (c) Dorsoventral patterning with dorsal gradients for BMP4 and WNT and with a ventral gradient of SHH (Sonic hedgehog). (d) Transverse section through the neural tube depicting various neurons specified by the gradient of SHH from the floor plate and the BMP4 and WNT from the roof plate: V0–3: interneurons and MN: motor neurons.