M. Yamamoto et al., The transcription factor FoxH1 (FAST) mediates Nodal signaling during anterior-posterior patterning and node formation in the mouse, GENE DEV, 15(10), 2001, pp. 1242-1256
FoxH1 (FAST) is a transcription factor that mediates signaling by transform
ing growth factor-beta, Activin, and Nodal. The role of FoxH1 in developmen
t has now been investigated by the generation and analysis of FoxH1-deficie
nt (FoxH1(-/-)) mice. The FoxH1(-/-) embryos showed various patterning defe
cts that recapitulate most of the defects induced by the loss of Nodal sign
aling. A substantial proportion of FoxH1(-/-) embryos failed to orient the
anterior-posterior (A-P) axis correctly, as do mice lacking Cripto, a corec
eptor for Nodal. In less severely affected FoxH1(-/-) embryos, A-P polarity
was established, but the primitive streak failed to elongate, resulting in
the lack of a definitive node and its derivatives. Heterozygosity for noda
l renders the FoxH1(-/-) phenotype more severe, indicative of a genetic int
eraction between FoxH1 and nodal. The expression of FoxH1 in the primitive
endoderm rescued the A-P patterning defects, but not the midline defects, o
f FoxH1(-/-) mice. These results indicate that a Nodal-FoxH1 signaling path
way plays a central role in A-P patterning and node formation in the mouse.