title: FoxH1 (Fast) functions to specify the anterior primitive streak in the mouse.
abstract: The node and the anterior visceral endoderm (AVE) are important organizing centers that pattern the mouse embryo by establishing the anterior-posterior (A-P), dorsal-ventral (D-V), and left-right (L-R) axes. Activin/nodal signaling through the Smad2 pathway has been implicated in AVE formation and in morphogenesis of the primitive streak, the anterior end of which gives rise to the node. The forkhead DNA-binding protein, FoxH1 (or Fast), functions as a Smad DNA-binding partner to regulate transcription in response to activin signaling. Here, we show that deletion of FoxH1 in mice results in failure to pattern the anterior primitive streak (APS) and form node, prechordal mesoderm, notochord, and definitive endoderm. In contrast, formation of the AVE can occur in the absence of FoxH1. The FoxH1 mutant phenotype is remarkably similar to that of mice deficient in the forkhead protein Foxa2 (HNF3beta), and we show that Foxa2 expression is dependent on FoxH1 function. These results show that FoxH1 functions in an activin/nodal-Smad signaling pathway that acts upstream of Foxa2 and is required specifically for patterning the APS and node in the mouse.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
authors.forename: P A
authors.initials: PA
authors.lastname: Hoodless
authors.forename: M
authors.initials: M
authors.lastname: Pye
authors.forename: C
authors.initials: C
authors.lastname: Chazaud
authors.forename: E
authors.initials: E
authors.lastname: Labbé
authors.forename: L
authors.initials: L
authors.lastname: Attisano
authors.forename: J
authors.initials: J
authors.lastname: Rossant
authors.forename: J L
authors.initials: JL
authors.lastname: Wrana
mesh_terms: D028341:Activins; D000818:Animals; D019521:Body Patterning; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051858:Forkhead Transcription Factors; D005775:Gastrula / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D007265:Inhibins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D016296:Mutagenesis; D055457:Nodal Protein; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D015398:Signal Transduction; D051899:Smad2 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C491117:Foxh1 protein, mouse; D055457:Nodal Protein; C526008:Nodal protein, mouse; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins