[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Heng, Julian Ik-Tsen; National Institute for Medical Research > Molecular Neurobiology
Nguyen, Laurent ; Université de Liège - ULiège > Département des sciences cliniques > Neurologie
Castro, Diogo S; National Institute for Medical Research > Molecular Neurobiology
Zimmer, Celine; National Institute for Medical Research > Molecular Neurobiology
Wildner, Hendrik; National Institute for Medical Research > Molecular Neurobiology
Armant, Olivier; National Institute for Medical Research > Molecular Neurobiology
Skowronska-Krawczyk, Dorota
Bedogni, Francesco
Matter, Jean-Marc
Hevner, Robert
Guillemot, Francois; National Institute for Medical Research > Molecular Neurobiology
Language :
English
Title :
Neurogenin 2 controls cortical neuron migration through regulation of Rnd2.
Publication date :
2008
Journal title :
Nature
ISSN :
0028-0836
eISSN :
1476-4687
Publisher :
Nature Publishing Group, Basingstoke, United Kingdom
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Fode, C. et al. A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons. Genes Dev. 14, 67-80 (2000).
Schuurmans, C. et al. Sequential phases of neocortical fate specification involve Neurogenin-dependent and -independent pathways. EMBO J. 23, 2892-2902 (2004).
Chardin, P. Function and regulation of Rnd proteins. Nature Rev. Mol. Cell Biol. 7, 54-62 (2006).
Marin, O. & Rubenstein, J. L. Cell migration in the forebrain. Annu. Rev. Neurosci. 26, 441-483 (2003).
Ayala, R., Shu, T. & Tsai, L. H. Trekking across the brain: the journey of neuronal migration. Cell 128, 29-43 (2007).
McManus, M. F. & Golden, J. A. Neuronal migration in developmental disorders. J. Child Neurol. 20, 280-286 (2005).
Loturco, J. J. & Bai, J. The multipolar stage and disruptions in neuronal migration. Trends Neurosci. 29, 407-413 (2006).
Bertrand, N., Castro, D. S. & Guillemot, F. Proneural genes and the specification of neural cell types. Nature Rev. Neurosci. 3, 517-530 (2002).
Ross, S. E., Greenberg, M. E. & Stiles, C. D. Basic helix-loop-helix factors in cortical development. Neuron 39, 13-25 (2003).
Hand, R. et al. Phosphorylation of Neurogenin2 specifies the migration properties and the dendritic morphology of pyramidal neurons in the neocortex. Neuron 48, 45-62 (2005).
Ge, W. et al. Coupling of cell migration with neurogenesis by proneural bHLH factors. Proc. Natl Acad. Sci. USA 103, 1319-1324 (2006).
Nguyen, L. et al. p27kip1 independently promotes neuronal differentiation and migration in the cerebral cortex. Genes Dev. 20, 1511-1524 (2006).
Mattar, P. et al. A screen for downstream effectors of Neurogenin2 in the embryonic neocortex. Dev. Biol. 273, 373-389 (2004).
Gohlke, J. M. et al. Characterization of the proneural gene regulatory network during mouse telencephalon development. BMC Biol. 6, 15 (2008).
Nobes, C. D. et al. A new member of the Rho family, Rnd1, promotes disassembly of actin filament structures and loss of cell adhesion. J. Cell Biol. 141, 187-197 (1998).
Negishi, M. & Katoh, H. Rho family GTPases and dendrite plasticity. Neuroscientist 11, 187-191 (2005).
Nakamura, K. et al. In vivo function of Rnd2 in the development of neocortical pyramidal neurons. Neurosci. Res. 54, 149-153 (2006).
Tabata, H. & Nakajima, K. Multipolar migration: the third mode of radial neuronal migration in the developing cerebral cortex. J. Neurosci. 23, 9996-10001 (2003).
Huang, H. P. et al. Regulation of the pancreatic islet-specific gene BETA2 (neuroD) by neurogenin 3. Mol. Cell. Biol. 20, 3292-3307 (2000).
Yokota, Y., Ring, C., Cheung, R., Pevny, L. & Anton, E. S. Nap1-regulated neuronal cytoskeletal dynamics is essential for the final differentiation of neurons in cerebral cortex. Neuron 54, 429-445 (2007).
Englund, C. et al. Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J. Neurosci. 25, 247-251 (2005).
Seo, S., Lim, J. W., Yellajoshyula, D., Chang, L. W. & Kroll, K. L. Neurogenin and NeuroD direct transcriptional targets and their regulatory enhancers. EMBO J., (2007).
Castro, D. S. et al. Proneural bHLH and Brn proteins co-regulate a neurogenic programme through cooperative binding to a conserved DNA motif. Dev. Cell 11, 831-844 (2006).
Ince-Dunn, G. et al. Regulation of thalamocortical patterning and synaptic maturation by NeuroD2. Neuron 49, 683-695 (2006).
Schwab, M. H. et al. Neuronal basic helix-loop-helix proteins (NEX and BETA2/Neuro D) regulate terminal granule cell differentiation in the hippocampus. J. Neurosci. 20, 3714-3724 (2000).
Chardin, P. GTPase regulation: getting aRnd Rock and Rho inhibition. Curr. Biol. 13, R702-R704 (2003).
Kakimoto, T., Katoh, H. & Negishi, M. Identification of splicing variants of Rapostlin, a novel RND2 effector that interacts with neural Wiskott-Aldrich syndrome protein and induces neurite branching. J. Biol. Chem. 279, 14104-14110 (2004).
Tanaka, H., Katoh, H. & Negishi, M. Pragmin, a novel effector of Rnd2 GTPase, stimulates RhoA activity. J. Biol. Chem. 281, 10355-10364 (2006).
Goebbels, S. et al. Genetic targeting of principal neurons in neocortex and hippocampus of NEX-Cre mice. Genesis 44, 611-621 (2006).
Bron, R. et al. Boundary cap cells constrain spinal motor neuron somal migration at motor exit points by a semaphoring-plexin mechanism. Neural Dev. 2, 21 (2007).
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.