Journal
DEVELOPMENTAL BIOLOGY
Volume 369, Issue 2, Pages 277-285Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2012.06.026
Keywords
Neurop lin; Semapl orin; Neural crest cell; Sympathetic nervous system; Heart; Aorta; Mouse
Categories
Funding
- UK Medical Research Council (MRC) [G070020]
- UK Biotechnology and Biological Sciences Research Council (BBSRC) [BB/1008373/1]
- UK British Heart Foundation [RG/10/10/28447, FS/07/031]
- BBSRC [BB/I008373/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/I008373/1] Funding Source: researchfish
- British Heart Foundation [RG/10/10/28447] Funding Source: researchfish
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The sympathetic nervous system (SNS) arises from neural crest (NC) cells during embryonic development and innervates the internal organs of vertebrates to modulate their stress response. NRP1 and NRP2 are receptors for guidance cues of the class 3 semaphorin (SEMA) family and are expressed in partially overlapping patterns in sympathetic NC cells and their progeny. By comparing the phenotypes of mice lacking NRP1 or its ligand SEMA3A with mice lacking NRP1 in the sympathetic versus vascular endothelial cell lineages, we demonstrate that SEMA3A signalling through NRP1 has multiple cell-autonomous roles in SNS development. These roles include neuronal cell body positioning, neuronal aggregation and axon guidance, first during sympathetic chain assembly and then to regulate the innervation of the heart and aorta. Loss of NRP2 or its ligand SEMA3F impaired sympathetic gangliogenesis more mildly than loss of SEMA3A/NRP1 signalling, but caused ectopic neurite extension along the embryonic aorta. The analysis of compound mutants lacking SEMA3A and SEMA3F or NRP1 and NRP2 in the SNS demonstrated that both signalling pathways cooperate to organise the SNS. We further show that abnormal sympathetic development in mice lacking NRP1 in the sympathetic lineage has functional consequences, as it causes sinus bradycardia, similar to mice lacking SEMA3A. (C) 2012 Elsevier Inc. All rights reserved.
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