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Identifier

000366322

Title

Μελέτη ενδοκυτταρίων και εξωκυτταρίων σημάτων κατα την ανάπτυξη των ενδονευρώνων στο φλοιό των εγκεφαλικών ημισφαιρίων

Alternative Title

Intracellular and extracellular modulators of cortical interneuron development

Author

Βιδάκη, Μαρίνα

Thesis advisor

Καραγωγέως, Δόμνα

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 involved are still unknown. Rac1, a member of the Rac subfamily of Rho GTPases, has been implicated in various aspects of cortical development such as cell cycle dynamics, axonogenesis and neuronal migration. In this study we have addressed the specific role of Rac1 in interneuron progenitors originating in the medial ganglionic eminence, the subpallial source of GABAergic interneurons, via Cre/loxP technology. Our findings show that in the absence of Rac1, 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 control cells. The absence of Rac1 from postmitotic interneurons does not result in obvious defects. These data indicate that a cell autonomous and stage-specific requirement of Rac1 activity within proliferating progenitors of cortical interneurons is necessary for their development. We have also assessed the extracellular signals that facilitate interneuron migration to the cortex during development. TAG1, a cell adhesion molecule of the IgSF, is expressed by the corticofugal fibers that are thought to serve as a scaffold for interneurons to migrate on, during embryogenesis. Using the promoter of the gene encoding for TAG1 as a genetic tool, we have generated two transgenic mouse lines, 3 to help us address questions regarding the role of corticofugal axons in interneuronal migration.

Language

Greek

Subject

Cell cycle

Cerebral cortex

Development

Interneurous

Migration

Nervous system

Ανάπτυξη

Ενδιάμεσοι νευρώνες

Κυτταρικός κύκλος