La transitine est une protéine cytosquelettique de la famille des filaments intermédiaires exprimée transitoirement dans les cellules progénitrices aviaires des tissus nerveux et musculaires. Lors de la myogenèse, la transitine est exprimée conjointement avec la vimentine dans les myoblastes et coexiste avec la desmine pendant une courte période de la différenciation puis elle devient absente dans les myotubes matures (Cossette et Vincent, 1991). Notre laboratoire travaille depuis plusieurs années sur l'expression et les caractéristiques biochimiques et moléculaires de cette protéine ainsi que sur son homologie avec la nestine de mammifères. Cependant, son rôle précis dans les cellules neurogéniques et myogéniques demeure inconnue. Récemment, une étude publiée par l'équipe de Wakamatsu (2007) a montré que la transitine est importante dans la régulation de la neurogenèse en agissant comme plateforme d'ancrage du déterminant d'identité cellulaire Numb et assurant la distribution asymétrique de cette protéine dans les cellules neuroépithéliales aviaires en mitose. Par contre, la fonction précise de cette protéine dans les cellules myogéniques reste inconnue jusqu'à ce jour.
Dans un premier temps, ce présent projet de maitrise visait à mettre en évidence le rôle de la transitine dans la distribution asymétrique de l'antagoniste de Notch, Numb, dans les cellules progénitrices des tissus musculaires par l'étude de la localisation fine de ces deux protéines dans le somite en différenciation. Les résultats ont montré que la transitine et Numb ne colocalisent que dans les cellules de la lèvre dorsale de dermomyotome qui sont des cellules progénitrices du tissu musculaire. Plus précisément, ces deux protéines colocalisent dans le coté basai des cellules mitotiques de la lèvre dorsale de dermomyotome. Nous proposons donc que la transitine est importante dans la régulation de la myogenèse en assurant la localisation asymétrique de Numb dans les cellules myogéniques en cours de la division. Ceci reste à être confirmé par des techniques microscopiques offrant une meilleure résolution que celles utilisées dans cette étude.
Dans un second temps, ce projet de maitrise a consisté à étudier l'effet de l'atténuation de l'expression de la transitine par interférence à l'ARN (ARNi) sur la différenciation myogénique dans un modèle cellulaire, la lignée QM7, afin de déterminer l'implication directe de la transitine durant la formation des muscles. Nous avons d'abord démontré
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que l'atténuation de l'expression de la transitine altère la morphologie cellulaire et influence la capacité des cellules de proliférer. La transitine peut donc jouer un rôle majeur dans le maintien de la structure de la cellule et de sa capacité de prolifération. Par la suite, nous avons démontré que l'atténuation de l'expression de la transitine altère la capacité des cellules de se fusionner, de se différencier et d'exprimer les marqueurs de la différenciation myogénique. Nos résultats ont montré qu'en absence de la transitine, les cellules gardent le caractère d'une cellule précurseur myogénique en exprimant les gènes précoces de la myogenèse d'une manière similaire avec celles cultivées dans un milieu de prolifération, après leur incubation dans un milieu de différenciation, alors qu'elles n'expriment pas le facteur de régulation myogénique, la myogenine, et les marqueurs des cellules musculaires matures, la desmine et la myosine. Selon ces résultats, nous avons proposé que la transitine puisse être impliquée dans la formation des muscles durant des étapes précoces de la myogenèse en aval de l'expression de MyoD et amont de l'expression de la myogenine.
Finalement, nous avons vérifié l'implication de Numb dans la régulation de la myogenèse des cellules dont l'expression de la transitine est diminuée. Nos résultats ont montré qu'en absence de la transitine, l'inhibition de la différenciation ne résulte pas de l'incapacité de Numb d'inhiber Notch et suggèrent par conséquent que la transitine est impliquée dans la régulation de la différenciation pendant une étape en aval de l'inhibition de Notch par Numb. Nos résultats ont aussi permis de supposer que cette protéine peut jouer un rôle clé dans la régulation de la synthèse/stabilité de Numb et que l'augmentation du niveau de Numb dans les cellules, dont l'expression de la transitine est diminuée, peut être à l'origine de l'inhibition de leur différenciation. En effet, nous avons constaté que le niveau d'expression de Numb est élevé dans ces cellules alors qu'aucun effet sur l'expression de l'ARNm n'a été observé.
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