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ZFIN ID: ZDB-PUB-180519-2
The Hippo pathway effector Wwtr1 regulates cardiac wall maturation in zebrafish
Lai, J.K.H., Collins, M.M., Uribe, V., Jiménez-Amilburu, V., Günther, S., Maischein, H.M., Stainier, D.Y.R.
Date: 2018
Source: Development (Cambridge, England)   145(10): (Journal)
Registered Authors: Maischein, Hans-Martin, Stainier, Didier
Keywords: Heart development, Hippo pathway, Taz, Trabeculation, Wwtr1, Yap
Microarrays: GEO:GSE103169
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Cell Proliferation/physiology
  • Heart/embryology*
  • Heart/growth & development*
  • Intercellular Junctions/physiology
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • Morpholinos/genetics
  • Myocytes, Cardiac/cytology*
  • Myosin Heavy Chains/genetics
  • Neuregulins/metabolism
  • Organogenesis/genetics
  • Organogenesis/physiology*
  • Protein-Serine-Threonine Kinases/metabolism
  • Receptor, ErbB-2/metabolism
  • Signal Transduction/physiology
  • Trans-Activators/metabolism
  • Troponin T/genetics
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 29773645 Full text @ Development
Cardiac trabeculation is a highly regulated process that starts with the delamination of compact layer cardiomyocytes. The Hippo signaling pathway has been implicated in cardiac development but many questions remain. We have investigated the role of Wwtr1, a nuclear effector of the Hippo pathway, in zebrafish and find that its loss leads to reduced cardiac trabeculation. However, in mosaic animals, wwtr1-/- cardiomyocytes contribute more frequently than wwtr1+/- cardiomyocytes to the trabecular layer of wild-type hearts. To investigate this paradox, we examined the myocardial wall at early stages and found that compact layer cardiomyocytes in wwtr1-/- hearts exhibit disorganized cortical actin structure and abnormal cell-cell junctions. Accordingly, wild-type cardiomyocytes in mosaic mutant hearts contribute less frequently to the trabecular layer than when present in mosaic wild-type hearts, indicating that wwtr1-/- hearts are not able to support trabeculation. We also found that Nrg/Erbb2 signaling, which is required for trabeculation, could promote Wwtr1 nuclear export in cardiomyocytes. Altogether, these data suggest that Wwtr1 establishes the compact wall architecture necessary for trabeculation, and that Nrg/Erbb2 signaling negatively regulates its nuclear localization and therefore its activity.