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 transforming growth factor-beta, Activin, and Nodal. The role of FoxH1 in development has now been investigated by the generation and analysis of FoxH1-deficient (FoxH1(-/-)) mice. The FoxH1(-/-) embryos showed various patterning defects that recapitulate most of the defects induced by the loss of Nodal signaling. A substantial proportion of FoxH1(-/-) embryos failed to orient the anterior-posterior (A-P) axis correctly, as do mice lacking Cripto, a coreceptor 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 nodal renders the FoxH1(-/-) phenotype more severe, indicative of a genetic interaction between FoxH1 and nodal. The expression of FoxH1 in the primitive endoderm rescued the A-P patterning defects, but not the midline defects, of FoxH1(-/-) mice. These results indicate that a Nodal-FoxH1 signaling pathway plays a central role in A-P patterning and node formation in the mouse.
Yamamoto
M
M
Division of Molecular Biology, Institute for Molecular and Cellular Biology, Osaka University, Japan.
Meno
C
C
Sakai
Y
Y
Shiratori
H
H
Mochida
K
K
Ikawa
Y
Y
Saijoh
Y
Y
Hamada
H
H
D000818:Animals; D019521:Body Patterning; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005314:Embryonic and Fetal Development; D004815:Epidermal Growth Factor; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D008562:Membrane Glycoproteins; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D055457:Nodal Protein; D010641:Phenotype; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C491117:Foxh1 protein, mouse; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D055457:Nodal Protein; C526008:Nodal protein, mouse; C489450:Tdgf1 protein, mouse; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor