Brachyury is required for elongation and vasculogenesis in the murine allantois.
Mouse conceptuses homozygous for mutations in brachyury (T) exhibit a short, misshapen allantois that fails to fuse with the chorion. Ultimately, mutant embryos die during mid-gestation. In the 60 years since this discovery, the role of T in allantoic development has remained obscure. T protein was recently identified in several new sites during mouse gastrulation, including the core of the allantois, where its function is not known. Here, using molecular, genetic and classical techniques of embryology, we have investigated the role of T in allantoic development. Conceptuses homozygous for the T(Curtailed) (T(C)) mutation (T(C)/T(C)) exhibited allantoic dysmorphogenesis shortly after the allantoic bud formed. Diminution in allantoic cell number and proliferation was followed by cell death within the core. Fetal liver kinase (Flk1)-positive angioblasts were significantly decreased in T(C)/T(C) allantoises and did not coalesce into endothelial tubules, possibly as a result of the absence of platelet endothelial cell adhesion molecule 1 (Pecam1), whose spatiotemporal relationship to Flk1 suggested a role in patterning the umbilical vasculature. Remarkably, microsurgical perturbation of the wild-type allantoic core phenocopied the T(C)/T(C) vascularization defect, providing further support that an intact core is essential for vascularization. Last, abnormalities were observed in the T(C)/T(C) heart and yolk sac, recently reported sites of T localization. Our findings reveal that T is required to maintain the allantoic core, which is essential for allantoic elongation and vascular patterning. In addition, morphological defects in other extraembryonic and embryonic vascular organs suggest a global role for T in vascularization of the conceptus.
Inman
Kimberly E
KE
Department of Anatomy, University of Wisconsin-Madison School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
Downs
Karen M
KM
D000482:Allantois / Q000166:cytology / Q000502:physiology*; D000818:Animals; D001006:Anus, Imperforate / Q000235:genetics; D017209:Apoptosis; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology*; D019521:Body Patterning / Q000502:physiology*; D002455:Cell Division; D005298:Fertility; D005326:Fetal Proteins / Q000502:physiology*; D006321:Heart / Q000196:embryology; D051379:Mice; D008940:Mitotic Index; D020825:T-Box Domain Proteins / Q000502:physiology*; D015017:Yolk Sac / Q000502:physiology; D000098908:Brachyury Protein
D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein