CUG-BP, Elav-like family member 1 (CELF1) is required for normal myofibrillogenesis, morphogenesis, and contractile function in the embryonic heart

Dev Dyn. 2016 Aug;245(8):854-73. doi: 10.1002/dvdy.24413. Epub 2016 May 31.

Abstract

Background: CUG-BP, Elav-like family member 1 (CELF1) is a multifunctional RNA binding protein found in a variety of adult and embryonic tissues. In the heart, CELF1 is found exclusively in the myocardium. However, the roles of CELF1 during cardiac development have not been completely elucidated.

Results: Myofibrillar organization is disrupted and proliferation is reduced following knockdown of CELF1 in cultured chicken primary embryonic cardiomyocytes. In vivo knockdown of Celf1 in developing Xenopus laevis embryos resulted in myofibrillar disorganization and a trend toward reduced proliferation in heart muscle, indicating conserved roles for CELF1 orthologs in embryonic cardiomyocytes. Loss of Celf1 also resulted in morphogenetic abnormalities in the developing heart and gut. Using optical coherence tomography, we showed that cardiac contraction was impaired following depletion of Celf1, while heart rhythm remained unperturbed. In contrast to cardiac muscle, loss of Celf1 did not disrupt myofibril organization in skeletal muscle cells, although it did lead to fragmentation of skeletal muscle bundles.

Conclusions: CELF1 is required for normal myofibril organization, proliferation, morphogenesis, and contractile performance in the developing myocardium. Developmental Dynamics 245:854-873, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: CELF1; Xenopus; chicken; development; heart; myofibrillogenesis; optical coherence tomography.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alternative Splicing / genetics
  • Animals
  • Blotting, Western
  • CELF1 Protein / genetics
  • CELF1 Protein / metabolism*
  • Cells, Cultured
  • Chick Embryo
  • Embryo, Nonmammalian / cytology*
  • Embryo, Nonmammalian / metabolism*
  • Heart / embryology
  • Immunohistochemistry
  • Morphogenesis / genetics
  • Morphogenesis / physiology
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Xenopus laevis

Substances

  • CELF1 Protein