Brachyury is required for elongation and vasculogenesis in the murine allantois
Autor: | Karen M. Downs, Kimberly E. Inman |
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Rok vydání: | 2006 |
Předmět: |
Fetal Proteins
Brachyury medicine.medical_specialty Apoptosis Biology Angioblast Anus Imperforate Mice Vasculogenesis Allantois Internal medicine medicine Mitotic Index Conceptus Animals Yolk sac Molecular Biology Body Patterning Yolk Sac Primitive streak Embryo Heart Cell biology medicine.anatomical_structure Endocrinology Fertility Blood Vessels T-Box Domain Proteins Cell Division Developmental Biology |
Zdroj: | Development (Cambridge, England). 133(15) |
ISSN: | 0950-1991 |
Popis: | 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. |
Databáze: | OpenAIRE |
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