Role of cardiac natriuretic peptides in seawater adaptation of medaka embryos as revealed by loss-of-function analysis

Hiroshi Miyanishi, Kataaki Okubo, Toyoji Kaneko, Yoshio Takei

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15 Citations (Scopus)


Cardiac natriuretic peptides (atrial natriuretic peptide, ANP; b-type natriuretic peptide, BNP; ventricular natriuretic peptide, VNP) and their direct ancestor C-type natriuretic peptide 3 (CNP3) exert potent osmoregulatory actions in fish. However, very little is known about their roles in embryonic osmoregulation. In this study, we performed loss-of-function analysis using euryhaline medaka (Oryzias latipes), which has lost ANP and VNP during evolution and thus possesses only BNP and CNP3. We found that the maintenance of whole-body osmolality in seawater embryos was impaired by the knockdown of BNPOLGC7 (BNP receptor) or CNP3 alone from 1 day postfertilization, and the CNP3 knockdown was accompanied by greater water loss. The impaired osmoregulation in the knockdown embryos was not due to the suppressed expression of major transporters for NaCl excretion via ionocytes or of key enzyme genes for metabolic water production, but to the impaired blood circulation to the yolk-sac membrane caused by abnormal heart development. We detected a strong positive correlation between impaired blood circulation and increased body fluid osmolality and pharmacological blockade of blood flow increased body fluid osmolality in seawater embryos. We also found that the exaggerated water loss in CNP3 knockdown embryos is related to the failure to suppress aquaporin (AQP3, AQP4, and AQP9) gene expression. These results show that CNP3 decrease water permeability of body surfaces and that both BNP and CNP3 ensure sufficient blood flow to the yolk-sac membrane for efficient salt excretion by ionocytes and sufficient water production by yolk metabolism to promote seawater adaptation during early development in medaka.

Original languageEnglish
Pages (from-to)R423-R434
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number6
Publication statusPublished - 2013
Externally publishedYes


  • Circulatory development
  • Embryonic osmoregulation
  • Gene knockdown
  • Ion secretion
  • Water regulation

ASJC Scopus subject areas

  • Medicine(all)


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