%0 Generic
%A Sanno, Hitomi
%D 2007
%F heidok:7261
%K Rho GTPase , brain development , transgenic mice
%R 10.11588/heidok.00007261
%T The generation and characterization of transgenic mice expressing modifiers of Rho GTPases
%U https://archiv.ub.uni-heidelberg.de/volltextserver/7261/
%X In developmental neurobiology, it is a fundamental topic but it is not still well investigated how newborn neurons elaborate axonal and dendrite processes to navigate complicated pathways and travel long distances before they reach their target.  Recent studies have suggested that Rho family GTP-binding proteins are important components of the signalling pathways that link the reception of extracellular cues to the cytoskeleton.  Rho family GTP-binding proteins regulate many different aspects of the actin cytoskeleton in a wide variety of organisms.  Small GTPases of the Rho family have been suggested to be involved in the regulation of formation of neurites and their differentiation into axons and dendrites, but the function of Rho GTPases is not still clear in terms of axonal and dendritic growth during mammalian development.  There are numerous data suggesting the important role of Rho GTPases in axonal guidance in vitro, however, there has been little direct evidence of these proteins in the in vivo context in mammals.  To modulate the activity of Rho during early nervous system development, we expressed either a RhoA dominant negative (N19-RhoA) mutant, a constitutively active (V14-RhoA) mutant, or a natural inhibitor, C3 transferase from Clostridium botulinum, in neuborn neurons under the control of the tau gene.  Their protein expression in neurons can be activated by application of Cre recombinase.  The tau gene was used because it is known to drive the high expression of genes specifically in neurons (Binder et al., 1995).  We used this transgenic strategy to analyze the effects of Rho family GTP-binding proteins on axonal outgrowth in early nervous system and the effect of long-term inhibition of Rho function in the adult brain.  The recombinant protein of N19-RhoA was expressed in the postnatal mouse brain, and we found that the somatosensory cortex in the adult mouse brain contained more severe involutions and aggregations of the cells in specific area of somatosensory cortex in brain, particularly in layer IV.  Also, the barrel-like discontinuous pattern was more extended toward the posterior part of the brain in the mice that have expressed a dominant negative RhoA.