Generating Diverse Spinal Motor Neuron Subtypes from Human Pluripotent Stem Cells

Figure 3

“Patterning” principles of the ventral neural tube by graded Sonic Hedgehog (Shh) signaling. Shh, shown in red, originates in the notochord (N) and floor plate (FP) and establishes a matrix of concentration-dependent positional identities, which are defined by particular combinatorial profiles of homeodomain transcription (HD) factors and basic helix-loop-helix (bHLH) transcription factors. Discrete ventral precursor domains are established by Shh-regulated transcription factor expression and divided into class I and class II factors based on their mode of regulation by Shh. These transcription factors are intermediaries in Shh-dependent ventral neural patterning. Cross-repressive interactions between class I and class II factors contribute to establishing individual precursor domains (P0–P3) with distinct boundaries as depicted. Each precursor domain gives rise to a specific class of postmitotic neurons. The cross-repressive class II factor counteracting Pax7 remains unresolved. Motor neurons are generated from the pMN domain.