A role for transcription factor glial cell missing 2 in Ca2+ homeostasis in zebrafish, Danio rerio

The present study investigated the role of the transcription factor, glial cell missing 2 (gcm2), in Ca2+ regulation in zebrafish larvae. Translational gene knockdown of gcm2 decreased Ca2+ uptake and the density of ionocytes expressing the epithelial Ca2+ channel (ecac), and disrupted the overall Ca2+ balance. Ca2+ uptake and the expression of gcm2 messenger RNA (mRNA) were significantly elevated in larvae acclimated to low Ca2+ water (25 μM); the stimulation of Ca2+ uptake was not observed in fish experiencing gcm2 knockdown. Acclimation to acidic water (pH 4) significantly reduced whole-body Ca2+ content owing to reduced Ca2+ uptake and increased Ca2+ efflux. However, ecac mRNA levels and the density of ecac-expressing ionocytes were increased in fish acclimated to acidic water, and maximal Ca2+ uptake capacity (J MAX) was significantly increased when measured in control water (pH ~7.4). Acclimation of larvae to acidic water significantly increased gcm2 mRNA expression, and in gcm2 morphants, no such stimulation in Ca2+ uptake was observed after their return to control water. Overexpression of gcm2 mRNA resulted in a significant increase in the numbers of ecac-expressing ionocytes and Ca2+ uptake. These observations reveal a critical role for gcm2 in Ca2+ homeostasis in zebrafish larvae.