dc.contributor.author | Sanno, Hitomi | |
dc.contributor.author | Shen, Xiao | |
dc.contributor.author | Kuru, Nilguen | |
dc.contributor.author | Bormuth, Ingo | |
dc.contributor.author | Bobsin, Kristin | |
dc.contributor.author | Gardner, Humphrey A. R. | |
dc.contributor.author | Komljenovic, Dorde | |
dc.contributor.author | Tarabykin, Victor | |
dc.contributor.author | Erzurumlu, Reha S. | |
dc.contributor.author | Tucker, Kerry L. | |
dc.date.accessioned | 2019-07-27T12:10:23Z | |
dc.date.accessioned | 2019-07-28T10:13:46Z | |
dc.date.available | 2019-07-27T12:10:23Z | |
dc.date.available | 2019-07-28T10:13:46Z | |
dc.date.issued | 2010 | |
dc.identifier.issn | 0270-6474 | |
dc.identifier.uri | https://dx.doi.org/10.1523/JNEUROSCI.3318-09.2010 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12418/9914 | |
dc.description | WOS: 000275950100006 | en_US |
dc.description | PubMed ID: 20335457 | en_US |
dc.description.abstract | Apoptosis of neurons in the maturing neocortex has been recorded in a wide variety of mammals, but very little is known about its effects on cortical differentiation. Recent research has implicated the RhoA GTPase subfamily in the control of apoptosis in the developing nervous system and in other tissue types. Rho GTPases are important components of the signaling pathways linking extracellular signals to the cytoskeleton. To investigate the role of the RhoA GTPase subfamily in neocortical apoptosis and differentiation, we have engineered a mouse line in which a dominant-negative RhoA mutant (N19-RhoA) is expressed from the Mapt locus, such that all neurons of the developing nervous system are expressing the N19-RhoA inhibitor. Postnatal expression of N19-RhoA led to no major changes in neocortical anatomy. Six layers of the neocortex developed and barrels (whisker-related neural modules) formed in layer IV. However, the density and absolute number of neurons in the somatosensory cortex increased by 12-26% compared with wild-type littermates. This was not explained by a change in the migration of neurons during the formation of cortical layers but rather by a large decrease in the amount of neuronal apoptosis at postnatal day 5, the developmental maximum of cortical apoptosis. In addition, overexpression of RhoA in cortical neurons was seen to cause high levels of apoptosis. These results demonstrate that RhoA-subfamily members play a major role in developmental apoptosis in postnatal neocortex of the mouse but that decreased apoptosis does not alter cortical cytoarchitecture and patterning. | en_US |
dc.description.sponsorship | German Research Foundation; University of Heidelberg; National Institutes of Health/National Institute of Neurological Disorders and Stroke [NS039050]; Max Planck Society; Heisenberg Program | en_US |
dc.description.sponsorship | This work was supported by the German Research Foundation [Deutsche Forschungsgemeinschaft: Sonderforschungsbereich 488, Teilprojekt B7/B9 (K. L. T.) and Exzellenzcluster 257 (V. T.)], the University of Heidelberg [Excellence Cluster Cellular Networks (K. L. T.)], National Institutes of Health/National Institute of Neurological Disorders and Stroke Grant NS039050 (R. S. E.), the Max Planck Society (V. T.), and the Heisenberg Program (V. T.). We thank Joachim Kirsch for generous scientific support, Karin Gorgas for enormous help with anatomical analysis, Yves-Alain Barde for thoughtful commentary on this manuscript, Silvia Arber for the floxed stop and Mapt targeting constructs, Frank Zimmermann for blastocyst injections, Stefan Offermanns for EIIa | en_US |
dc.language.iso | eng | en_US |
dc.publisher | SOC NEUROSCIENCE | en_US |
dc.relation.isversionof | 10.1523/JNEUROSCI.3318-09.2010 | en_US |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.title | Control of Postnatal Apoptosis in the Neocortex by RhoA-Subfamily GTPases Determines Neuronal Density | en_US |
dc.type | article | en_US |
dc.relation.journal | JOURNAL OF NEUROSCIENCE | en_US |
dc.contributor.department | [Sanno, Hitomi -- Shen, Xiao -- Bobsin, Kristin -- Komljenovic, Dorde -- Tucker, Kerry L.] Univ Heidelberg, Inst Anat, D-69120 Heidelberg, Germany -- [Sanno, Hitomi -- Shen, Xiao -- Bobsin, Kristin -- Tucker, Kerry L.] Univ Heidelberg, Interdisciplinary Ctr Neurosci, D-69120 Heidelberg, Germany -- [Kuru, Nilguen] Cumhuriyet Univ, Dept Biol, Fac Educ, TR-58140 Sivas, Turkey -- [Kuru, Nilguen -- Erzurumlu, Reha S.] Univ Maryland, Dept Anat & Neurobiol, Sch Med, Baltimore, MD 21201 USA -- [Bormuth, Ingo -- Tarabykin, Victor] Max Planck Inst Expt Med, D-37075 Gottingen, Germany -- [Bormuth, Ingo -- Tarabykin, Victor] Charite, Inst Cell Biol & Neurobiol, D-10098 Berlin, Germany -- [Gardner, Humphrey A. R.] Novartis Inst BioMed Res, Cambridge, MA 02139 USA | en_US |
dc.identifier.volume | 30 | en_US |
dc.identifier.issue | 12 | en_US |
dc.identifier.endpage | 4231 | en_US |
dc.identifier.startpage | 4221 | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |