| Přispěvatelé: |
UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - Faculté de pharmacie et des sciences biomédicales, Clotman, Frédéric, Hermans, Emmanuel, Jossin, Yves, Rezsohazy, René, Lanuza, Guillermo |
| Popis: |
Locomotion is a complex behavior regulated by circuits, named central pattern generators, located in the ventral part of the spinal cord. These circuits are composed of motor neurons (MNs) and of different populations of interneurons: dorsal dI6 and ventral V0 to V3 cardinal populations. During development, they are produced from specific progenitor domains distributed along the dorso-ventral axis of the spinal cord. The p2 progenitor domain generates V2 interneurons that diversify at least into five populations: V2a, V2b, V2c, V2d and Pax6-V2 interneurons. This differentiation process involves fine genetic regulations and cross-repressive mechanisms that consolidate cell fate. Indeed, progenitor domains of V2 interneurons and of MNs are closely adjacent during development and share some molecular determinants. Cross and mutual repressions between Ceh-10 homeobox (Chx10) gene, expressed in differentiating V2a interneurons, and Homeobox 9 (Hb9), expressed in early MNs, participate in the consolidation of V2 interneuron versus MN identity by preventing the activation of inappropriate differentiation program. However, Chx10 starts to be expressed in differentiating V2a interneurons. Therefore, we could address the following question: which factor secures the identity of V2 interneurons at early stages of development. Studies demonstrate that the unique paralog gene of Chx10, the Visual System homeoboX 1 (Vsx1), is also present in V2 interneuron compartment in a more medial part of the spinal cord. The aim of my thesis project is to characterize the expression profile of Vsx1 in the spinal and determine whether it may, in collaboration with its paralog Chx10, contribute to the securisation of V2 interneuron identity. In this work, we show that Vsx1 transiently labels an intermediate V2 precursor compartment. We provide evidence that this transcription factor is not necessary for V2 interneuron production but contributes to their development. We show that the unique paralog factor of Chx10 identically prevents motor neuron differentiation in early V2 precursors. Furthermore, combined inactivation unveiled cooperativity between Vsx1 and Chx10 although they are not produced in the same cells. (BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2019 |
