Long-range guidance of spinal commissural axons by netrin1 and sonic hedgehog from midline floor plate cells

An important model for axon pathfinding is provided by guidance of embryonic commissural axons from dorsal spinal cord to ventral midline floor plate (FP). FP cells produce a chemoattractive activity, comprised largely of netrin1 (FP-netrin1) and Sonic hedgehog (Shh), that can attract the axons at a...

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Detalles Bibliográficos
Autores: Wu, Zhuhao, Makihara, Shirin, Yam, Patricia T., Teo, Shaun, Renier, Nicolas, Balekoglu, Nursen, Moreno-Bravo, Juan Antonio, Olsen, Olav, Chédotal, Alain, Charron, Frédéric, Tessier-Lavigne, Marc
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/308987
Acceso en línea:http://hdl.handle.net/10261/308987
Access Level:acceso abierto
Palabra clave:Axon guidance
Long-range guidance
Netrin1
Sonic hedgehog
Chemoattraction
Haptotaxis
Commissural neurons
Spinal cord
Descripción
Sumario:An important model for axon pathfinding is provided by guidance of embryonic commissural axons from dorsal spinal cord to ventral midline floor plate (FP). FP cells produce a chemoattractive activity, comprised largely of netrin1 (FP-netrin1) and Sonic hedgehog (Shh), that can attract the axons at a distance in vitro. netrin1 is also produced by ventricular zone (VZ) progenitors along the axons’ route (VZ-netrin1). Recent studies using region-specific netrin1 deletion suggested that FP-netrin1 is dispensable and VZ-netrin1 sufficient for netrin guidance activity in vivo. We show that removing FP-netrin1 actually causes guidance defects in spinal cord consistent with long-range action (i.e., over hundreds of micrometers), and double mutant analysis supports that FP-netrin1 and Shh collaborate to attract at long range. We further provide evidence that netrin1 may guide via chemotaxis or haptotaxis. These results support the model that netrin1 signals at both short and long range to guide commissural axons in spinal cord.