Autophagy is essential for cardiac morphogenesis during vertebrate development

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