Autophagy is essential for cardiac morphogenesis during vertebrate development

Eunmyong Lee, Yeon Koo, Aylwin Ng, Yongjie Wei, Kate Luby-Phelps, Amy Juraszek, Ramnik J. Xavier, Ondine Cleaver, Beth Levine, James F. Amatruda

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Genetic analyses indicate that autophagy, an evolutionarily conserved lysosomal degradation pathway, is essential for eukaryotic differentiation and development. However, little is known about whether autophagy contributes to morphogenesis during embryogenesis. To address this question, we examined the role of autophagy in the early development of zebrafish, a model organism for studying vertebrate tissue and organ morphogenesis. Using zebrafish that transgenically express the fluorescent autophagy reporter protein, GFP-LC3, we found that autophagy is active in multiple tissues, including the heart, during the embryonic period. Inhibition of autophagy by morpholino knockdown of essential autophagy genes (including atg5, atg7, and becn1) resulted in defects in morphogenesis, increased numbers of dead cells, abnormal heart structure, and reduced organismal survival. Further analyses of cardiac development in autophagy-deficient zebrafish revealed defects in cardiac looping, abnormal chamber morphology, aberrant valve development, and ectopic expression of critical transcription factors including foxn4, tbx5, and tbx2. Consistent with these results, Atg5 -deficient mice displayed abnormal Tbx2 expression and defects in valve development and chamber septation. Thus, autophagy plays an essential, conserved role in cardiac morphogenesis during vertebrate development.

Original languageEnglish (US)
Pages (from-to)572-587
Number of pages16
JournalAutophagy
Volume10
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • Autophagy
  • Heart development
  • Zebrafish
  • atg5
  • atg7
  • becn1
  • tbx2

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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