Control of Postnatal Apoptosis in the Neocortex byRhoA-Subfamily GTPases Determines Neuronal Density

Neurons 0301 basic medicine Afferent Pathways 0303 health sciences 571 Green Fluorescent Proteins Age Factors Gene Expression Regulation, Developmental Apoptosis Cell Count Cell Differentiation Mice, Transgenic Neocortex Embryo, Mammalian GTP Phosphohydrolases 3. Good health Mice, Inbred C57BL Mice 03 medical and health sciences Animals, Newborn Cell Movement Mutation Animals Humans Genes, Dominant
DOI: 10.1523/jneurosci.3318-09.2010 Publication Date: 2010-03-24T17:08:00Z
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 theMaptlocus, 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.
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