title: An autocrine Wnt5a-Ror signaling loop mediates sympathetic target innervation.
abstract: During nervous system development, axon branching at nerve terminals is an essential step in the formation of functional connections between neurons and target cells. It is known that target tissues exert control of terminal arborization through secretion of trophic factors. However, whether the in-growing axons themselves produce diffusible cues to instruct target innervation remains unclear. Here, we use conditional mutant mice to show that Wnt5a derived from sympathetic neurons is required for their target innervation in vivo. Conditional deletion of Wnt5a resulted in specific deficits in the extension and arborization of sympathetic fibers in their final target fields, while no defects were observed in the overall tissue patterning, proliferation, migration or differentiation of neuronal progenitors. Using compartmentalized neuronal cultures, we further demonstrate that the Ror receptor tyrosine kinases are required locally in sympathetic axons to mediate Wnt5a-dependent branching. Thus, our study suggests an autocrine Wnt5a-Ror signaling pathway that directs sympathetic axon branching during target innervation.
authors: Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
authors: Yun Kyoung
authors: YK
authors: Ryu
authors: Sarah Ellen
authors: SE
authors: Collins
authors: Hsin-Yi Henry
authors: HY
authors: Ho
authors: Haiqing
authors: H
authors: Zhao
authors: Rejji
authors: R
authors: Kuruvilla
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D001369:Axons / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D004622:Embryo, Mammalian / Q000166:cytology / Q000294:innervation* / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D019426:Integrases / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000196:embryology*; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein / Q000378:metabolism
chemical_list: D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein; C438615:Wnt5a protein, mouse; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C045073:Cre recombinase; D019426:Integrases