The transcription factor FoxH1 (FAST) mediates Nodal signaling during anterior-posterior patterning and node formation in the mouse

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.