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Article Dans Une Revue eLife Année : 2022

Transient regulation of focal adhesion via Tensin3 is required for nascent oligodendrocyte differentiation

Emeric Merour
  • Fonction : Auteur
Hatem Hmidan
  • Fonction : Auteur
Corentine Marie
  • Fonction : Auteur
Pierre-Henri Helou
  • Fonction : Auteur
Haiyang Lu
  • Fonction : Auteur
Antoine Potel
  • Fonction : Auteur
Jean-Baptiste Hure
  • Fonction : Auteur
Adrien Clavairoly
  • Fonction : Auteur
Yi Ping Shih
  • Fonction : Auteur
Salman Goudarzi
  • Fonction : Auteur
Sebastien Dussaud
Sassan Hafizi
Su Hao Lo
Bassem Hassan
Carlos Parras

Résumé

The differentiation of oligodendroglia from oligodendrocyte precursor cells (OPCs) to complex and extensive myelinating oligodendrocytes (OLs) is a multistep process that involves large-scale morphological changes with significant strain on the cytoskeleton. While key chromatin and transcriptional regulators of differentiation have been identified, their target genes responsible for the morphological changes occurring during OL myelination are still largely unknown. Here, we show that the regulator of focal adhesion, Tensin3 (Tns3), is a direct target gene of Olig2, Chd7, and Chd8, transcriptional regulators of OL differentiation. Tns3 is transiently upregulated and localized to cell processes of immature OLs, together with integrin-β1, a key mediator of survival at this transient stage. Constitutive Tns3 loss of function leads to reduced viability in mouse and humans, with surviving knockout mice still expressing Tns3 in oligodendroglia. Acute deletion of Tns3 in vivo, either in postnatal neural stem cells (NSCs) or in OPCs, leads to a twofold reduction in OL numbers. We find that the transient upregulation of Tns3 is required to protect differentiating OPCs and immature OLs from cell death by preventing the upregulation of p53, a key regulator of apoptosis. Altogether, our findings reveal a specific time window during which transcriptional upregulation of Tns3 in immature OLs is required for OL differentiation likely by mediating integrin-β1 survival signaling to the actin cytoskeleton as OL undergo the large morphological changes required for their terminal differentiation.

Dates et versions

hal-03854771 , version 1 (16-11-2022)

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Emeric Merour, Hatem Hmidan, Corentine Marie, Pierre-Henri Helou, Haiyang Lu, et al.. Transient regulation of focal adhesion via Tensin3 is required for nascent oligodendrocyte differentiation. eLife, 2022, 11, ⟨10.7554/eLife.80273⟩. ⟨hal-03854771⟩
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