Bcl-wav and the mitochondrial calcium uniporter drive gastrula morphogenesis in zebrafish.

TitleBcl-wav and the mitochondrial calcium uniporter drive gastrula morphogenesis in zebrafish.
Publication TypeJournal Article
Year of Publication2013
AuthorsPrudent, J, Popgeorgiev, N, Bonneau, B, Thibaut, J, Gadet, R, Lopez, J, Gonzalo, P, Rimokh, R, Manon, S, Houart, C, Herbomel, P, Aouacheria, A, Gillet, G
JournalNat Commun
Date Published2013
KeywordsActins, Amino Acid Sequence, Animals, Apoptosis, Biological Transport, Blastomeres, Calcium, Calcium Channels, Cell Movement, Cells, Cultured, Gastrula, Gastrulation, Gene Knockdown Techniques, Green Fluorescent Proteins, HeLa Cells, Humans, Mice, Mitochondria, Molecular Sequence Data, Morphogenesis, Morpholinos, Notochord, Proto-Oncogene Proteins c-bcl-2, Sequence Alignment, Sequence Analysis, DNA, Voltage-Dependent Anion Channel 1, Zebrafish

Bcl-2 proteins are acknowledged as key regulators of programmed cell death. However, increasing data suggest additional roles, including regulation of the cell cycle, metabolism and cytoskeletal dynamics. Here we report the discovery and characterization of a new Bcl-2-related multidomain apoptosis accelerator, Bcl-wav, found in fish and frogs. Genetic and molecular studies in zebrafish indicate that Bcl-wav and the recently identified mitochondrial calcium uniporter (MCU) contribute to the formation of the notochord axis by controlling blastomere convergence and extension movements during gastrulation. Furthermore, we found that Bcl-wav controls intracellular Ca(2+) trafficking by acting on the mitochondrial voltage-dependent anion channel, and possibly on MCU, with direct consequences on actin microfilament dynamics and blastomere migration guidance. Thus, from an evolutionary point of view, the original function of Bcl-2 proteins might have been to contribute in controlling the global positioning system of blastomeres during gastrulation, a critical step in metazoan development.

Alternate JournalNat Commun
Citation Key10.1038/ncomms3330
PubMed ID23942336
Grant List089701 / / Wellcome Trust / United Kingdom