title: Candidate gene approach identifies multiple genes and signaling pathways downstream of Tbx4 in the developing allantois.
abstract: Loss of Tbx4 results in absence of chorio-allantoic fusion and failure of formation of the primary vascular plexus of the allantois leading to embryonic death at E10.5. We reviewed the literature for genes implicated in chorio-allantoic fusion, cavitation and vascular plexus formation, processes affected in Tbx4 mutant allantoises. Using this candidate gene approach, we identified a number of genes downstream of Tbx4 in the allantois including extracellular matrix molecules Vcan, Has2, and Itgα5, transcription factors Snai1 and Twist, and signaling molecules Bmp2, Bmp7, Notch2, Jag1 and Wnt2. In addition, we show that the canonical Wnt signaling pathway contributes to the vessel-forming potential of the allantois. Ex vivo, the Tbx4 mutant phenotype can be rescued using agonists of the Wnt signaling pathway and, in wildtype allantoises, an inhibitor of the canonical Wnt signaling pathway disrupts vascular plexus formation. In vivo, Tbx4 and Wnt2 double heterozygous placentas show decreased vasculature suggesting interactions between Tbx4 and the canonical Wnt signaling pathway in the process of allantois-derived blood vessel formation.
authors.affiliation: Department of Genetics and Development, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Ripla
authors.initials: R
authors.lastname: Arora
authors.forename: Chelsea M
authors.initials: CM
authors.lastname: del Alcazar
authors.forename: Edward E
authors.initials: EE
authors.lastname: Morrisey
authors.forename: L A
authors.initials: LA
authors.lastname: Naiche
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Papaioannou
mesh_terms: D000482:Allantois / Q000378:metabolism*; D000818:Animals; D003433:Crosses, Genetic; D005109:Extracellular Matrix; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D051379:Mice; D009154:Mutation; D011247:Pregnancy; D011270:Pregnancy, Animal; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D020825:T-Box Domain Proteins; C103177:Tbx4 protein, mouse; D051153:Wnt Proteins