Dishevelled-associated activator of morphogenesis 1 (Daam1) is required for heart morphogenesis

Deqiang Li, Mark A. Hallett, Wuqiang Zhu, Michael Rubart-von der Lohe, Ying Liu, Zhenyun Yang, Hanying Chen, Laura Haneline, Rebecca Chan, Robert J. Schwartz, Loren Field, Simon J. Atkinson, Weinian Shou

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Dishevelled-associated activator of morphogenesis 1 (Daam1), a member of the formin protein family, plays an important role in regulating the actin cytoskeleton via mediation of linear actin assembly. Previous functional studies of Daam1 in lower species suggest its essential role in Drosophila trachea formation and Xenopus gastrulation. However, its in vivo physiological function in mammalian systems is largely unknown. We have generated Daam1-deficient mice via gene-trap technology and found that Daam1 is highly expressed in developing murine organs, including the heart. Daam1-deficient mice exhibit embryonic and neonatal lethality and suffer multiple cardiac defects, including ventricular noncompaction, double outlet right ventricles and ventricular septal defects. In vivo genetic rescue experiments further confirm that the lethality of Daam1-deficient mice results from the inherent cardiac abnormalities. In-depth analyses have revealed that Daam1 is important for regulating filamentous actin assembly and organization, and consequently for cytoskeletal function in cardiomyocytes, which contributes to proper heart morphogenesis. Daam1 is also found to be important for proper cytoskeletal architecture and functionalities in embryonic fibroblasts. Biochemical analyses indicate that Daam1 does not regulate cytoskeletal organization through RhoA, Rac1 or Cdc42. Our study highlights a crucial role for Daam1 in regulating the actin cytoskeleton and tissue morphogenesis.

Original languageEnglish
Pages (from-to)303-315
Number of pages13
JournalDevelopment (Cambridge)
Volume138
Issue number2
DOIs
StatePublished - Jan 15 2011

Fingerprint

Morphogenesis
Actin Cytoskeleton
Actins
Double Outlet Right Ventricle
Gastrulation
Ventricular Heart Septal Defects
Xenopus
Trachea
Cardiac Myocytes
Drosophila
Fibroblasts
Technology
Genes

Keywords

  • Actin
  • Congenital heart defects
  • Cytoskeletal architecture
  • Daam1
  • Formin protein
  • Heart development
  • Mouse
  • Planar cell polarity (PCP)
  • Sarcomere organization

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Dishevelled-associated activator of morphogenesis 1 (Daam1) is required for heart morphogenesis. / Li, Deqiang; Hallett, Mark A.; Zhu, Wuqiang; Rubart-von der Lohe, Michael; Liu, Ying; Yang, Zhenyun; Chen, Hanying; Haneline, Laura; Chan, Rebecca; Schwartz, Robert J.; Field, Loren; Atkinson, Simon J.; Shou, Weinian.

In: Development (Cambridge), Vol. 138, No. 2, 15.01.2011, p. 303-315.

Research output: Contribution to journalArticle

Li, Deqiang ; Hallett, Mark A. ; Zhu, Wuqiang ; Rubart-von der Lohe, Michael ; Liu, Ying ; Yang, Zhenyun ; Chen, Hanying ; Haneline, Laura ; Chan, Rebecca ; Schwartz, Robert J. ; Field, Loren ; Atkinson, Simon J. ; Shou, Weinian. / Dishevelled-associated activator of morphogenesis 1 (Daam1) is required for heart morphogenesis. In: Development (Cambridge). 2011 ; Vol. 138, No. 2. pp. 303-315.
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