PUBLICATION

Tension heterogeneity directs form and fate to pattern the myocardial wall

Authors
Priya, R., Allanki, S., Gentile, A., Mansingh, S., Uribe, V., Maischein, H.M., Stainier, D.Y.R.
ID
ZDB-PUB-201120-165
Date
2020
Source
Nature   588(7836): 130-134 (Journal)
Registered Authors
Maischein, Hans-Martin, Stainier, Didier
Keywords
none
MeSH Terms
  • Actomyosin/metabolism
  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Feedback, Physiological*
  • Heart/anatomy & histology*
  • Heart/embryology*
  • Models, Animal
  • Myocardium/cytology*
  • Myocytes, Cardiac/cytology*
  • Organogenesis*
  • Receptors, Notch/metabolism
  • Signal Transduction
  • Zebrafish/anatomy & histology
  • Zebrafish/embryology*
PubMed
33208950 Full text @ Nature
Abstract
How diverse cell fates and complex forms emerge and feed back to each other to sculpt functional organs remains unclear. In the developing heart, the myocardium transitions from a simple epithelium to an intricate tissue that consists of distinct layers: the outer compact and inner trabecular layers. Defects in this process, which is known as cardiac trabeculation, cause cardiomyopathies and embryonic lethality, yet how tissue symmetry is broken to specify trabecular cardiomyocytes is unknown. Here we show that local tension heterogeneity drives organ-scale patterning and cell-fate decisions during cardiac trabeculation in zebrafish. Proliferation-induced cellular crowding at the tissue scale triggers tension heterogeneity among cardiomyocytes of the compact layer and drives those with higher contractility to delaminate and seed the trabecular layer. Experimentally, increasing crowding within the compact layer cardiomyocytes augments delamination, whereas decreasing it abrogates delamination. Using genetic mosaics in trabeculation-deficient zebrafish models-that is, in the absence of critical upstream signals such as Nrg-Erbb2 or blood flow-we find that inducing actomyosin contractility rescues cardiomyocyte delamination and is sufficient to drive cardiomyocyte fate specification, as assessed by Notch reporter expression in compact layer cardiomyocytes. Furthermore, Notch signalling perturbs the actomyosin machinery in cardiomyocytes to restrict excessive delamination, thereby preserving the architecture of the myocardial wall. Thus, tissue-scale forces converge on local cellular mechanics to generate complex forms and modulate cell-fate choices, and these multiscale regulatory interactions ensure robust self-organized organ patterning.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping