Long-range Ca2+ signaling from growth cone to soma mediates reversal of neuronal migration induced by slit-2.
Neuronal migration and growth-cone extension are both guided by extracellular factors in the developing brain, but whether these two forms of guidance are mechanistically linked is unclear. Application of a Slit-2 gradient in front of the leading process of cultured cerebellar granule cells led to the collapse of the growth cone and the reversal of neuronal migration, an event preceded by a propagating Ca(2+) wave from the growth cone to the soma. The Ca(2+) wave was required for the Slit-2 effect and was sufficient by itself to induce the reversal of migration. The Slit-2-induced reversal of migration required active RhoA, which was accumulated at the front of the migrating neuron, and this polarized RhoA distribution was reversed during the migration reversal induced by either the Slit-2 gradient or the Ca(2+) wave. Thus, long-range Ca(2+) signaling coordinates the Slit-2-induced changes in motility at two distant parts of migrating neurons by regulating RhoA distribution.
Guan
Chen-Bing
CB
Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Xu
Hua-Tai
HT
Jin
Ming
M
Yuan
Xiao-Bing
XB
Poo
Mu-Ming
MM
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002465:Cell Movement; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D020439:Growth Cones / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000098552:Slit Homolog 2 Protein
D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D020742:rhoA GTP-Binding Protein; D000098552:Slit Homolog 2 Protein; D002118:Calcium