Dact1 is expressed during chicken and mouse skeletal myogenesis and modulated in human muscle diseases

Renata Erbert Contriciani, Fernanda Cristina da Veiga, Mariana Juliani do Amaral, Bianca Gazieri Castelucci, Lizandra Maia de Sousa, Marcelo Bispo de Jesus, Sílvio Roberto Consonni, Carla Beatriz Collares-Buzato, Cláudia Mermelstein, Susanne Dietrich, Lúcia Elvira Alvares

Research output: Contribution to journalArticlepeer-review

Abstract

Vertebrate skeletal muscle development and repair relies on the precise control of Wnt signaling. Dact1 (Dapper/Frodo) is an important modulator of Wnt signaling, interacting with key components of the various Wnt transduction pathways. Here, we characterized Dact1 mRNA and protein expression in chicken and mouse fetal muscles in vivo and during the differentiation of chick primary and mouse C2C12 myoblasts in vitro. We also performed in silico analysis to investigate Dact1 gene expression in human myopathies, and evaluated the Dact1 protein structure to seek an explanation for the accumulation of Dact1 protein aggregates in the nuclei of myogenic cells.

Our results show for the first time that in both chicken and mouse, Dact1 is expressed during myogenesis, with a strong upregulation as cells engage in terminal differentiation, cell cycle withdrawal and cell fusion. In humans, Dact1 expression was found to be altered in specific muscle pathologies, including muscular dystrophies. Our bioinformatic analyses of Dact1 proteins revealed long intrinsically disordered regions, which may underpin the ability of Dact1 to interact with its many partners in the various Wnt pathways. In addition, we found that Dact1 has strong propensity for liquid-liquid phase separation, a feature that explains its ability to form nuclear aggregates and points to a possible role as a molecular ‘on’-‘off’ switch.

Taken together, our data suggest Dact1 as a candidate, multi-faceted regulator of amniote myogenesis with a possible pathophysiological role in human muscular diseases.
Original languageEnglish
Article number110645
Number of pages13
JournalComparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology
Volume256
Early online date9 Jul 2021
DOIs
Publication statusPublished - 1 Oct 2021

Keywords

  • Dact1
  • skeletal myogenesis
  • wnt signaling
  • chicken primary myoblast
  • C2C12 cells
  • intrinsically disordered proteins
  • muscular diseases

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