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Published June 14, 2002 | Supplemental Material
Journal Article Open

Sensory Nerves Determine the Pattern of Arterial Differentiation and Blood Vessel Branching in the Skin


Nerves and blood vessels are branched structures, but whether their branching patterns are established independently or coordinately is not clear. Here we show that arteries, but not veins, are specifically aligned with peripheral nerves in embryonic mouse limb skin. Mutations that eliminate peripheral sensory nerves or Schwann cells prevent proper arteriogenesis, while those that disorganize the nerves maintain the alignment of arteries with misrouted axons. In vitro, sensory neurons or Schwann cells can induce arterial marker expression in isolated embryonic endothelial cells, and VEGF^(164/120) is necessary and sufficient to mediate this induction. These data suggest that peripheral nerves provide a template that determines the organotypic pattern of blood vessel branching and arterial differentiation in the skin, via local secretion of VEGF.

Additional Information

© 2002 Cell Press. Under an Elsevier user license. Received: December 11, 2001; Revised: April 9, 2002. We thank Dr. T. Yagi for Sema3A mutants, Dr. C. Birchmeier for her collaboration and support, H. Sanchez and K.F. Lee for rescued erbB2 mutant embryos, N. Grillet and J.F. Brunet for Phox2b mutants, and M. Gertsenstein and A. Nagy for VEGF-lacZ mice. We also thank F. Guillemot for providing Ngn2 mutants, A.L. Kolodkin for providing anti-NP1 antibody, and T. Müller for providing anti-BFABP antibody. Thanks to R. Diamond and P. Koen for FACS assistance, S. Pease, B. Kennedy, and the staff of the Transgenic Animal Facility at Caltech for assistance with mouse breeding and care, G. Mosconi for laboratory management, J. Yamada for technical support, and G. Mancuso for administrative assistance. Thanks also to S. Gerety for invaluable help, discussion, and constructive comments on the manuscript and L. Lo and other Anderson lab members for technical help and discussion. D.J.A. is an Investigator of the Howard Hughes Medical Institute. This work was supported in part by National Institutes of Health grant HL66221.

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