Aspects biochimiques et cellulaires de la dérégulation du processus myogénique chez des souris hypomorphes pour le gène Pofut I

Abstract : Postnatal muscle growth in mice mainly occurs by hypertrophy and by anincrease of myofibres length. This increase in myofibres area is controlled by multiple signaling pathways such as Notch signaling, which is involved in activation of satellite cells (SC) at the beginning of postnatal muscle growth in mice. The O-fucosylation of EGF-like repeats within the extracellular domain of NOTCH receptors, mediated by protein O-fucosyltransferase 1 (POFUT1), plays a key role in the modulation of receptor-ligand interactions (R-L), necessary for activation of Notch signaling. Pofut1cax/cax mice are hypomorphic for the Pofut1 gene. In addition to skeletal defects, our results show postnatal muscular hypertrophy, no hyperplasia and a reduced pool of SC. To understand the origin of this hypertrophy, primary cultures of myoblasts derived from SC (SCDM) from skeletal muscles were studied in proliferating and differentiating conditions. Pofut1cax/cax SCDM showed a reduced Notch signaling due to aless efficient R-L interactions provoked by a low O-fucosylation of EGF-like repeats. This results in decreased expression of Pax7, a marker of undifferentiated state, and a change in the expression of myogenic regulatory factors (Myod, Myf5 and Myogenin). Subsequently, the proportion of Pax7+/MyoD- progenitors decreased while the proportion of Pax7-/MyoD+ cells committed in differentiation increased. These findings corroborate early differentiation of Pofut1cax/cax SCDM.Our results indicate that this postnatal muscle hypertrophy in Pofut1cax/caxmice is due to the fact that activated satellite cells are more prone todifferentiate and fuse with pre-existing myofibres that returning toquiescence.
Document type :
Theses
Complete list of metadatas

https://tel.archives-ouvertes.fr/tel-01428814
Contributor : Abes Star <>
Submitted on : Friday, January 6, 2017 - 3:26:07 PM
Last modification on : Monday, September 24, 2018 - 9:42:06 AM
Long-term archiving on : Friday, April 7, 2017 - 3:02:23 PM

File

2016LIMO0086.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-01428814, version 1

Collections

Citation

Bilal Al Jaam. Aspects biochimiques et cellulaires de la dérégulation du processus myogénique chez des souris hypomorphes pour le gène Pofut I. Médecine humaine et pathologie. Université de Limoges, 2016. Français. ⟨NNT : 2016LIMO0086⟩. ⟨tel-01428814⟩

Share

Metrics

Record views

118

Files downloads

220