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ETUDE FONCTIONNELLE DU GENE GATA2 AU COURS DE LA NEUROGENESE DANS LA MOELLE EPINIERE VENTRALE EMBRYONNAIRE

Abstract : Our project is dedicated to the functional analysis of the transcription factor GATA2, which is involved in the specification of several neuronal populations in the nervous system. My work was mainly focused on the study of Gata2 function during the neurogenesis in the embryonic spinal cord.
In the ventral spinal cord, motor neurons and 4 types of interneurons (V0, V1, V2 and V3) are generated in distinct territories. V2 interneurons are specified in a territory close to motor neurons and are subdivided into V2a and V2b. Our aims were to identify the role of Gata2 during V2 interneuron specification and to determine its influence on the proliferation of the neuronal precursor cells.
By loss- and gain-of-function experiments, we have shown that:
1. Gata2 inhibits the proliferation of neuronal precursor cells, by inhibiting the cell cycle and by repressing the Notch pathway. This control can be uncoupled from neuronal differentiation and does not require a proneural activity.
2. Gata2 promotes V2 differentiation and represses motor neuron differentiation by interfering with Shh and TGF-Β pathways. In addition, Gata2 participates in the V2 dichotomy since it promotes V2b, but inhibits V2a, differentiation. Moreover, we have shown that V2a are glutamatergics whereas V2b are GABAergics.
This study has contributed to highlight the complexity of the molecular mechanisms which participate in the amplification of the diversity of neuronal populations.
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Submitted on : Tuesday, October 30, 2007 - 5:55:25 PM
Last modification on : Wednesday, December 9, 2020 - 3:08:14 PM
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  • HAL Id : tel-00184253, version 1

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Cédric Francius. ETUDE FONCTIONNELLE DU GENE GATA2 AU COURS DE LA NEUROGENESE DANS LA MOELLE EPINIERE VENTRALE EMBRYONNAIRE. Biologie cellulaire. Université Pierre et Marie Curie - Paris VI, 2007. Français. ⟨tel-00184253⟩

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