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Fig. 2. Secreted signals establish the dorsal-ventral pattern of progenitor domains in the neural tube by regulating the spatial expression of transcription factors. (A) Schematic of a transverse section of an amniote embryo. Within the spinal cord, functionally distinct neurons are generated in a spatially segregated manner in response to signals emanating from within the neural tube and surrounding tissue. The key signals include Shh (red), secreted by the notochord and floor plate; retinoic acid (RA, green), produced by the somites that flank the neural tube; and BMP and Wnt family members (blue), which are produced dorsally. The spread of Shh from ventral to dorsal establishes a gradient of activity within the ventral neural tube (red dots). (B) Schematic of the ventral half of the neural tube, where the ventral gradient of Shh activity controls position identity by regulating the expression, in neural progenitors, of a set of transcription factors. These include Pax7, Pax6 and Irx3, which are repressed by Shh signaling, and Dbx1, Dbx2, Nkx6.1, Olig2, Nkx2.2 and Foxa2, which require Shh signaling for their expression. The differential response of these genes to graded Shh signaling establishes distinct dorsal and ventral boundaries of expression for each factor. The combinatorial expression of the transcription factors defines domains of progenitors (p). From the ventral pole, these are termed FP (floor plate), p3, pMN and p2-p0. Each progenitor domain is identified by its transcription factor code, and this code determines the neuronal subtype progeny the progenitors produce. Each progenitor domain generates different ventral (V) interneuron subtypes (V0-V3) or motoneurons (MN). Consequently, the spatially segregated production of distinct neuronal subtypes is determined by the DV pattern of transcription factor expression in progenitors. The ventral boundary of the progenitor domain for dorsal interneurons dI6 (pD6) illustrates the range of Shh signaling in the ventral neural tube. (C) The three ventral-most progenitor domains of the neural tube, FP, p3 and pMN, can be identified by the expression of the transcription factors, Foxa2, Nkx2.2 and Olig2, respectively. The onset of expression of the three transcription factors follows a dorsal-to-ventral progression, resulting in the temporally distinct establishment of each progenitor domain. Initially, ventrally located progenitors express Olig2 prior to the initiation of Nkx2.2 and Foxa2. As the expression domain of Olig2 expands dorsally, Nkx2.2 and Foxa2 are induced ventrally. Olig2 is then downregulated in cells expressing Nkx2.2. Hence, Nkx2.2 expression defines the ventral limit of the Olig2-expressing, pMN domain. Subsequently, in cells of the ventral midline, Nkx2.2 expression is downregulated by an as yet undefined mechanism. This generates a Nkx2.2⁺ Foxa2^- p3 domain, and a Foxa2⁺ Nkx2.2^- FP. One consequence of the progressive induction and modification of ventral progenitor identity is that Nkx2.2- and Olig2-expressing cells share a lineage (Dessaud et al., 2007).

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