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Ca2+ signaling has been reported to play a key role in the differentiation of many cell types including vertebrate skeletal muscle.Recent work from our lab has characterized the Ca2+ signals generated during the development of slow muscle cells(SMCs)in intact zebrafish,and provided evidence that Ca2+ release is mediated via both inositol trisphosphate receptors and ryanodine receptors.Here,I present new data,which suggest that in zebrafish embryos,a novel member of the voltage-gated channel superfamily,the two pore channel 2(TPC2;which is known to be located in the membranes of acidic organelles and is activated by NAADP),also plays a crucial role in the differentiation of SMCs.Using a line of transgenic zebrafish that express the Ca2+-sensitive bioluminescent protein aequorin specifically in skeletal muscle cells,morpholino(MO)-based knockdown of TPC2 resulted in a significant attenuation of the Ca2+ signals and gross morphological changes in the trunk musculature.Embryos treated with the inhibitor of TPCs(trans-Ned-19)or of the vacuolar-type H+ ATPase that depletes the Ca2+ store in acidic organelles(bafilomycin A1),resulted in a disrupted pattern of Ca2+ signals as well as an altered morphology of the SMCs.I also show that TPC2 is expressed in a striated pattern in the SMCs at 24 hours post fertilization.Together,these data provide evidence to suggest that TPC2-mediated Ca2+ release might initiate the sarcoplasmic reticulum-generated Ca2+ transients shown to be essential for myofibrilogenesis as well as for the overall development of the trunk musculature.Supported by RGC awards: HKUST662211 and 662113,and TBRS award: T13-706/11-1.