| Abstract |
Cortical GABAergic interneurons provide inhibitory input to the pyramidal cells and are
characterized by extraordinary neurochemical and functional diversity. Their dysfunction and
abnormal development have been associated with severe disorders, like autism, epilepsy and
schizophrenia. Although recent studies have uncovered some of the molecular components ,
underlying interneuron development, including the cellular and molecular mechanisms guiding their
migration to the cortex, the intracellular components invovlved are still unknown.
Rac1, a member of the Rac subfamily of Rho GTPases , have been implicated in various
aspects of cortical development such as cell cycle dynamics , axonogenesis , and neuronal
migration. Rac3 has an almost identical sequence with Rac1 but is specificaly expressed in the
nerve system. Recent data from our lab have adressed the specific role of Rac1 in interneuron
progenitors originating in the medial ganglionic eminence (MGE), the subpallial source of
GABAergic interneurons, via Cre/loxP technology. In the absence of Rac, only half of GABAergic
interneurons populate the cortex. Their progenitors are delayed in exiting the cell cycle and as a
consequence migrate towards the pallium later than controll cells.
The partial loss of the interneurons suggests the antistathmistic role of another molecule.
By examinining double mutants for Rac1 and Rac3 it is possible to determine whether the
synergistic effects of Rac1 and Rac3 mutants reflect qualitatively-distinct effects of these Rho
GTPases or rather quantitative effects of their combine activities. In this sudy we examine the
migration in Rac1, Rac3 and Rac1/Rac3 mutants. We observe that during early embryonic stages
the Rac1/Rac3 phenotype is similar to the Rac1. Later on Rac1/Rac3 mutants interneurons have a
more severe deffect in the migration. Loss of both Rac1 and Rac3 GTPases cause defects in actin
and microtubule dynamics.
Finally, in this study we tried to culture cortical interneurons in 3D scaffolds that can better
represent in vivo cellular behavior.
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O ρόλος των μικρών Rho GTPασών,Rac1 και Rac3 στην ανάπτυξη των ενδονευρώνων του φλοιού.In vitro και in vivo ανάλυση
