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Fig. 10. Summary of proposed role for Foxa2, Nodal and Hh signalling pathways in
ventral CNS development. The model is based upon data in this paper and in
other papers cited in the text. Nodal signalling induces MFP through Madh/Smad
and FoxH1/Fast/Sur transcription factors. This occurs in the absence of Foxa2
function, implicating other factors downstream of Nodal in the earliest
induction of floorplate identity. Nodal signalling induces foxa2
expression in MFP and Foxa2 function is required for differentiation of these
cells. Hh genes are among those requiring Foxa2 function for maintained
expression. However, as Hh genes are initially expressed in
mol-/- embryos, we suggest that other transcription
factors, including Madh2/FoxH1, contribute to the presence of Hh proteins in
the ventral neural tube. The only known role for Hh proteins in the MFP is to
maintain expression of differentiation markers. Hh signals working through Gli
proteins induce foxa2 expression in the LFP. Foxa2 activity is
required for proper formation of the LFP and this is likely to be due both to
non-autonomous roles (e.g. regulation of Hh production in the MFP), and
activity within the LFP itself. Hh activity also spreads further to induce and
pattern adjacent ventral CNS cell types, including cranial motoneurones and
serotonergic raphé neurones. In the absence of Foxa2 function, Hh
activity leads to ectopic dorsal expression of several Hh pathway target
genes. This implies that Foxa2 may also negatively regulate the dorsal spread
of Hh activity within the ventral CNS.
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