The forkhead transcription factor Foxf1 is required for differentiation of extra-embryonic and lateral plate mesoderm.
The murine Foxf1 gene encodes a forkhead transcription factor expressed in extra-embryonic and lateral plate mesoderm and later in splanchnic mesenchyme surrounding the gut and its derivatives. We have disrupted Foxf1 and show that mutant embryos die at midgestation due to defects in mesodermal differentiation and cell adhesion. The embryos do not turn and become deformed by the constraints of a small, inflexible amnion. Extra-embryonic structures exhibit a number of differentiation defects: no vasculogenesis occurs in yolk sac or allantois; chorioallantoic fusion fails; the amnion does not expand with the growth of the embryo, but misexpresses vascular and hematopoietic markers. Separation of the bulk of yolk sac mesoderm from the endodermal layer and adherence between mesoderm of yolk sac and amnion, indicate altered cell adhesion properties and enhanced intramesodermal cohesion. A possible cause of this is misexpression of the cell-adhesion protein VCAM1 in Foxf1-deficient extra-embryonic mesoderm, which leads to co-expression of VCAM with its receptor, alpha(4)-integrin. The expression level of Bmp4 is decreased in the posterior part of the embryo proper. Consistent with this, mesodermal proliferation in the primitive streak is reduced and somite formation is retarded. Expression of Foxf1 and the homeobox gene Irx3 defines the splanchnic and somatic mesodermal layers, respectively. In Foxf1-deficient embryos incomplete separation of splanchnic and somatic mesoderm is accompanied by misexpression of Irx3 in the splanchnopleure, which implicates Foxf1 as a repressor of Irx3 and as a factor involved in coelom formation.
Mahlapuu
M
M
Department of Molecular Biology, Göteborg University, The Lundberg Laboratory, Medicinaregatan 9C, Box 462, S-405 30 Göteborg, Sweden.
Ormestad
M
M
Enerbäck
S
S
Carlsson
P
P
D000482:Allantois / Q000166:cytology; D000650:Amnion / Q000166:cytology; D000818:Animals; D001483:Base Sequence; D001808:Blood Vessels / Q000196:embryology; D002454:Cell Differentiation; D002455:Cell Division; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005313:Fetal Death / Q000235:genetics; D015870:Gene Expression; D018390:Gene Targeting; D017403:In Situ Hybridization; D008297:Male; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D015017:Yolk Sac / Q000098:blood supply
D017931:DNA Primers; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1