santa and valentine pattern concentric growth of cardiac myocardium in the zebrafish

Mably, J.D., Chuang, L.P., Serluca, F.C., Mohideen, M.A., Chen, J.N., and Fishman, M.C.
Development (Cambridge, England)   133(16): 3139-3146 (Journal)
Registered Authors
Chen, Jau-Nian, Chuang, Lesley, Fishman, Mark C., Mably, John, Mohideen, Manzoor Pallithotangal, Serluca, Fabrizio
santa, valentine, Myocardial growth, Cerebral cavernous malformations, CCM
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Body Patterning/genetics
  • Cell Count
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • Embryonic Development/genetics
  • Endocardium/cytology
  • Endocardium/embryology
  • Gene Expression Regulation
  • Genes, Lethal
  • Heart/embryology
  • Heart Defects, Congenital/embryology*
  • Heart Defects, Congenital/genetics
  • Heart Defects, Congenital/metabolism
  • Membrane Glycoproteins/metabolism*
  • Molecular Sequence Data
  • Muscle Proteins/genetics
  • Muscle Proteins/metabolism*
  • Mutation
  • Myocardium/cytology
  • Myocardium/metabolism
  • RNA, Messenger/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
16873582 Full text @ Development
During embryogenesis, the myocardial layer of the primitive heart tube grows outward from the endocardial-lined lumen, with new cells added to generate concentric thickness to the wall. This is a key evolutionary step, demarcating vertebrates from more primitive chordates, and is essential for normal cardiac function. Zebrafish embryos with the recessive lethal mutations santa (san) and valentine (vtn) do not thicken, but do add the proper number of cells to the myocardium. Consequently, the heart chambers are huge, constituted of a monolayered myocardium lined by endocardium. This phenotype is similar to that of the heart of glass (heg) mutation, which we described previously as a novel endocardial expressed gene. By positional cloning, we here identify san as the zebrafish homolog of human CCM1, and vtn as the homolog of human CCM2. Dominant mutations of either in humans cause vascular anomalies in the brain, known as cerebral cavernous malformations. The synergistic effects of morpholino pairs indicate that san, vtn and heg are in a genetic pathway, and san and vtn contain protein motifs, NPxY and PTB domain, respectively, known to interact. This suggests that concentric growth of the myocardium, crucial for blood pressure generation, is dictated by a heg-san-vtn signaling pathway.
Genes / Markers
Show all Figures
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes