Inactivation of the Sema5a Gene Results in Embryonic Lethality and Defective Remodeling of the Cranial Vascular System

Abstract

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.

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Correction for Fiore et al., “Inactivation of the Sema5a Gene Results in Embryonic Lethality and Defective Remodeling of the Cranial Vascular System”

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://mcb.asm.org/.

ACKNOWLEDGMENTS

We thank Corrie de Gier-de Vries, Gisela Pott, and Maria Wenning for expert technical assistance.

The 2H3 antibody developed by Thomas M. Jessel was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the Department of Biological Sciences, University of Iowa, Iowa City. This work was supported by grants from the DFG to A.W.P.