Neurogenin 2 controls cortical neuron migration through regulation of Rnd2.
Motility is a universal property of newly generated neurons. How cell migration is coordinately regulated with other aspects of neuron production is not well understood. Here we show that the proneural protein neurogenin 2 (Neurog2), which controls neurogenesis in the embryonic cerebral cortex, directly induces the expression of the small GTP-binding protein Rnd2 (ref. 3) in newly generated mouse cortical neurons before they initiate migration. Rnd2 silencing leads to a defect in radial migration of cortical neurons similar to that observed when the Neurog2 gene is deleted. Remarkably, restoring Rnd2 expression in Neurog2-mutant neurons is sufficient to rescue their ability to migrate. Our results identify Rnd2 as a novel essential regulator of neuronal migration in the cerebral cortex and demonstrate that Rnd2 is a major effector of Neurog2 function in the promotion of migration. Thus, a proneural protein controls the complex cellular behaviour of cell migration through a remarkably direct pathway involving the transcriptional activation of a small GTP-binding protein.
Heng
Julian Ik-Tsen
JI
Division of Molecular Neurobiology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
Nguyen
Laurent
L
Castro
Diogo S
DS
Zimmer
Céline
C
Wildner
Hendrik
H
Armant
Olivier
O
Skowronska-Krawczyk
Dorota
D
Bedogni
Francesco
F
Matter
Jean-Marc
JM
Hevner
Robert
R
Guillemot
François
F
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D048430:Cell Shape; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D034622:RNA Interference; D020741:rho GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D020413:3' Untranslated Regions; D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D020741:rho GTP-Binding Proteins; C102938:Neurog2 protein, mouse; C475019:Rnd2 protein, mouse