| Abstract |
The forebrain comprises an intricate set of structures that are required for some of the most complex and evolved functions of the mammalian brain. As a reflection of its compexity, specification of different neuronal cell types is remarakbly precise and cell migration in the forebrain is extremely elaborate.
During the formation of the cerebral cortex, cortical non pyramidal cells, the GABAergic interneurons, are generated in the medial ganglionic eminence (MGE) of the ventral telencephalon and migrate tangentially to the dorsal telencephalon. Although several genes that play a role in the specification and the migration of these cells have been identified, the underlying molecular and cellular mechanism is not fully understood.
The present study forms part of a project that intends to examine the role of Rac1 on the development of cortical inhibitory interneurons. Rac1 belongs to the family of Rho GTPases, a
group of proteins that are intracellular signal transducers known to regulate multiple signalling pathways. Rho GTPases therefore mediate a variety of cellular functions, including cellular migration and specification. For the aim of our study, Rac1 was specifically deleted, using the Cre-LoxP method, from GABAergic interneurons, at the progenitor stage as well as post-mitotically, by using different Cre lines. When Rac1 is deleted in progenitors we observe delayed migration of interneurons as well as reduced numbers of these cells in the adult cortex. On the contrary, no similar phenotype is observed when Rac1 is deleted in post-mitotic interneurons. These findings suggest that Rac1 plays a role in the development of these cells during the progenitor stage, whereas it seems to be ispensable for cellular motility per se during neuronal migration.
An additional aim is to explore whether Rac3 compensates for Rac1 function. In order to address this issue we specifically deleted Rac1 from interneuron progenitors in Rac3 knockout mice, generating mice with interneurons lacking both proteins. Even greater reduction of the numbers of GABAergic interneurons is observed in these mice, suggesting that some functional compensation between the two molecules exists.
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Μελέτη του ρόλου της GTPάσης RAC1 στην αναπτύξη των GABAεργικών ενδονευρώνων του φλοιού
