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

Autor: Patricia T. Yam, Olav Olsen, Marc Tessier-Lavigne, Alain Chédotal, Zhuhao Wu, Shaun Teo, Frédéric Charron, Nicolas Renier, Juan Antonio Moreno-Bravo, Nursen Balekoglu, Shirin Makihara
Přispěvatelé: Kavli Foundation, Rockefeller University, Agency for Science, Technology and Research A*STAR (Singapore), Leon Levy Foundation, Stanford University, Agence Nationale de la Recherche (France), Canadian Institutes of Health Research, Canada Foundation for Innovation
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Popis: 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.
Z.W. was supported by the Kavli Neural Systems Institute at The Rockefeller University. S.M. was supported by a Keidanren Ishizaka Memorial Foundation fellowship. S.T. was supported by fellowship funds from the Agency for Science, Technology and Research, Singapore (A∗STAR). N.R. was supported by a post-doctoral fellowship from the Shelby White – Leon Levy Foundation. Work performed in the M.T.-L. laboratory was supported by The Rockefeller University and Stanford University, work performed in the A.C. laboratory was supported by a grant from the Agence Nationale de la Recherche (ANR-14-CE13-0004-01), and work performed in the F.C. laboratory was supported by the Canadian Institutes of Health Research (CIHR FDN334023), the Fonds de Recherche du Québec - Santé (FRQS), and the Canada Foundation for Innovation (CFI 33768). F.C. holds the Canada Research Chair in Developmental Neurobiology.
Databáze: OpenAIRE