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ZFIN ID: ZDB-PUB-080309-14
High-speed imaging of developing heart valves reveals interplay of morphogenesis and function
Scherz, P.J., Huisken, J., Sahai-Hernandez, P., and Stainier, D.Y.
Date: 2008
Source: Development (Cambridge, England)   135(6): 1179-1187 (Journal)
Registered Authors: Stainier, Didier
Keywords: Cardiovascular development, Cox2 (Ptgs2), Microscopy, Prostaglandins, SPIM, Zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Cyclooxygenase 2/genetics
  • Cyclooxygenase 2/physiology
  • Cyclooxygenase 2 Inhibitors/pharmacology
  • DNA Primers/genetics
  • Dinoprost/antagonists & inhibitors
  • Dinoprost/genetics
  • Dinoprost/physiology
  • Heart Valves/drug effects
  • Heart Valves/embryology*
  • Heart Valves/physiology
  • Microscopy, Fluorescence
  • Morphogenesis
  • Signal Transduction
  • Thromboxane A2/antagonists & inhibitors
  • Thromboxane A2/genetics
  • Thromboxane A2/physiology
  • Transforming Growth Factor beta/antagonists & inhibitors
  • Transforming Growth Factor beta/genetics
  • Transforming Growth Factor beta/physiology
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/physiology
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology
PubMed: 18272595 Full text @ Development
Knowing how mutations disrupt the interplay between atrioventricular valve (AVV) morphogenesis and function is crucial for understanding how congenital valve defects arise. Here, we use high-speed fluorescence microscopy to investigate AVV morphogenesis in zebrafish at cellular resolution. We find that valve leaflets form directly through a process of invagination, rather than first forming endocardial cushions. There are three phases of valve function in embryonic development. First, the atrioventricular canal (AVC) is closed by the mechanical action of the myocardium, rolls together and then relaxes. The growing valve leaflets serve to block the canal during the roll and, depending on the developmental stage, either expand or hang down as a leaflet to block the canal. These steps are disrupted by the subtle morphological changes that result from inhibiting ErbB-, TGFbeta-or Cox2 (Ptgs2)-dependent signaling. Cox2 inhibition affects valve development due to its effect on myocardial cell size and shape, which changes the morphology of the ventricle and alters valve geometry. Thus, different signaling pathways regulate distinct aspects of the behavior of individual cells during valve morphogenesis, thereby influencing specific facets of valve function.