Abstract
The development of a patterned vasculature is essential for normal organogenesis. We found that signaling by semaphorin 3E (Sema3E) and its receptor plexin-D1 controls endothelial cell positioning and the patterning of the developing vasculature in the mouse. Sema3E is highly expressed in developing somites, where it acts as a repulsive cue for plexin-D1-expressing endothelial cells of adjacent intersomitic vessels. Sema3E-plexin-D1 signaling did not require neuropilins, which were previously presumed to be obligate Sema3 coreceptors. Moreover, genetic ablation of Sema3E or plexin-D1 but not neuropilin-mediated Sema3 signaling disrupted vascular patterning. These findings reveal an unexpected semaphorin signaling pathway and define a mechanism for controlling vascular patterning.
Publication types
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Animals
- Binding Sites
- Blood Vessels / embryology*
- Blood Vessels / metabolism
- Body Patterning
- COS Cells
- Chick Embryo
- Chlorocebus aethiops
- Cytoskeletal Proteins
- Endothelial Cells / cytology
- Endothelial Cells / physiology
- Endothelium, Vascular / cytology
- Endothelium, Vascular / embryology
- Glycoproteins / metabolism*
- In Situ Hybridization
- Intracellular Signaling Peptides and Proteins
- Ligands
- Membrane Glycoproteins / metabolism*
- Membrane Proteins / metabolism*
- Mice
- Morphogenesis
- Mutation
- Nerve Tissue Proteins / metabolism*
- Neuropilin-1 / metabolism
- Neuropilin-2 / metabolism
- Phenotype
- Protein Binding
- Recombinant Fusion Proteins / metabolism
- Semaphorins
- Signal Transduction
- Somites / metabolism*
- Transfection
Substances
- Cytoskeletal Proteins
- Glycoproteins
- Intracellular Signaling Peptides and Proteins
- Ligands
- Membrane Glycoproteins
- Membrane Proteins
- Nerve Tissue Proteins
- Neuropilin-2
- Plxnd1 protein, mouse
- Recombinant Fusion Proteins
- Sema3e protein, mouse
- Semaphorins
- Neuropilin-1