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XB-ART-45897
J Biol Chem October 12, 2012; 287 (42): 35565-35575.
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Kcnh1 voltage-gated potassium channels are essential for early zebrafish development.

Stengel R , Rivera-Milla E , Sahoo N , Ebert C , Bollig F , Heinemann SH , Schönherr R , Englert C .


Abstract
The Kcnh1 gene encodes a voltage-gated potassium channel highly expressed in neurons and involved in tumor cell proliferation, yet its physiological roles remain unclear. We have used the zebrafish as a model to analyze Kcnh1 function in vitro and in vivo. We found that the kcnh1 gene is duplicated in teleost fish (i.e. kcnh1a and kcnh1b) and that both genes are maternally expressed during early development. In adult zebrafish, kcnh1a and kcnh1b have distinct expression patterns but share expression in brain and testis. Heterologous expression of both genes in Xenopus oocytes revealed a strong conservation of characteristic functional properties between human and fish channels, including a unique sensitivity to intracellular Ca(2+)/calmodulin and modulation of voltage-dependent gating by extracellular Mg(2+). Using a morpholino antisense approach, we demonstrate a strong kcnh1 loss-of-function phenotype in developing zebrafish, characterized by growth retardation, delayed hindbrain formation, and embryonic lethality. This late phenotype was preceded by transcriptional up-regulation of known cell-cycle inhibitors (p21, p27, cdh2) and down-regulation of pro-proliferative factors, including cyclin D1, at 70% epiboly. These results reveal an unanticipated basic activity of kcnh1 that is crucial for early embryonic development and patterning.

PubMed ID: 22927438
PMC ID: PMC3471731
Article link: J Biol Chem


Species referenced: Xenopus laevis
Genes referenced: arnt eef1a2 egr2 kcnh1 kcnh2 kcnh5 mia3 myod1 tp53 znrd2


Article Images: [+] show captions
References [+] :
Amores, Zebrafish hox clusters and vertebrate genome evolution. 1998, Pubmed