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Fig. 7. The neural tube gene regulatory network. (A) Selective
cross-repressive interactions contribute to the spatial-temporal regulation of
gene expression in the neural tube. (Upper panel) Cross-repression between
Nkx6 and Dbx proteins generate distinct gene expression patterns in p0, p1 and
p2 domains of progenitors. (Lower panel) The generation of p2, pMN and p3
domains depends on selective cross-repressive interactions between Pax6 and
Nkx2.2, and Olig2 and Irx3, and on the repression of Olig2 by Nkx2.2.
(B) Schematic of DV patterning through repressive interactions.
Representative transverse sections through mouse spinal cord are shown (RF,
roof plate; FP, floor plate). The identification of regulatory modules that
contain binding sites for POU, Sox and HD transcription factors adjacent to
many genes of the neural tube GRN has led to a model for the regulation of
these genes. POU (green) and Sox (blue) factors are transcriptional activators
that are broadly expressed in neural progenitors (bottom panel, green), thus
they are believed to provide spatially unrestricted activation to the
regulatory modules. The HD factors (red), which have spatially and temporally
restricted expression patterns in neural progenitors (example in bottom
panel), mostly function as transcriptional repressors and have therefore been
proposed to provide repressive input to the modules. The combination of
uniform positive input and spatially restricted negative input on a target
gene (yellow) would generate a spatially restricted pattern of expression
(bottom panel). In this model, the consequences of mutating the repressive HD
gene would be the derepression of the target gene (bottom panel, right).
(C) Alterations in the pattern of gene expression in embryos lacking
individual members of the neural tube GRN confirm the importance of
cross-repressive interactions for DV pattern formation. The changes in gene
expression in mouse embryos mutant for the indicated genes are summarized in
the diagrams. In Nkx6.1-/- embryos, Nkx6.2 (6.2) and Dbx2
(D2) are expressed in more-ventral progenitors. Dbx1 (D1) expands ventrally in
Nkx6.2-/- mutants. Deletion of both Nkx6.1 and Nkx6.2
results in the ventral expansion of both Dbx1 and Dbx2. In
Olig2-/- mouse embryos, Irx3 expands into the domain
normally occupied by MN progenitors. Olig2 (O2) expands ventrally in
Nkx2.2-/- embryos. In embryos mutant for Pax6,
Nkx2.2 (2.2) expands dorsally, repressing Olig2 expression (Irx3 expression
has not been determined).
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