Inactivation of the Sema5a gene results in embryonic lethality and defective remodeling of the cranial vascular system.
The semaphorins are a large family of proteins involved in the patterning of both the vascular and the nervous systems. In order to analyze the function of the membrane-bound semaphorin 5A (Sema5A), we generated mice homozygous for a null mutation in the Sema5a gene. Homozygous null mutants die between embryonic development days 11.5 (E11.5) and E12.5, indicating an essential role of Sema5A during embryonic development. Mutant embryos did not show any morphological defects that could account for the lethality of the mutation. A detailed analysis of the vascular system uncovered a role of Sema5A in the remodeling of the cranial blood vessels. In Sema5A null mutants, the complexity of the hierarchically organized branches of the cranial cardinal veins was decreased. Our results represent the first genetic analysis of the function of a class 5 semaphorin during embryonic development and identify a role of Sema5A in the regional patterning of the vasculature.
Fiore
Roberto
R
Abteilung Molekularbiologie, Institut für Allgemeine Zoologie und Genetik, Westfälische Wilhelms-Universität Münster, Schlossplatz 5, D-48149 Münster, Germany.
Rahim
Belquis
B
Christoffels
Vincent M
VM
Moorman
Antoon F M
AF
Püschel
Andreas W
AW
D000818:Animals; D019521:Body Patterning; D002550:Cerebral Veins / Q000002:abnormalities / Q000196:embryology; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000166:cytology; D020868:Gene Silencing; D005804:Genes, Lethal / Q000235:genetics*; D006720:Homozygote; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D039961:Semaphorins; D012886:Skull / Q000098:blood supply*; D013234:Stem Cells / Q000502:physiology; D014680:Veins / Q000196:embryology*
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C103619:Sema5A protein, mouse; D039961:Semaphorins
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