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

• Published in: Nature communications Vol. 4; no. 1; p. 2330
• Main Authors: Prudent, Julien, Popgeorgiev, Nikolay, Bonneau, Benjamin, Thibaut, Julien, Gadet, Rudy, Lopez, Jonathan, Gonzalo, Philippe, Rimokh, Ruth, Manon, Stephen, Houart, Corinne, Herbomel, Philippe, Aouacheria, Abdel, Gillet, Germain
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 2013; Nature Publishing Group
• Subjects: 631/136/1660/2127; 631/80/86; Actins - genetics; Amino Acid Sequence; Animals; Apoptosis - genetics; Biological Transport - genetics; Blastomeres - metabolism; Calcium - metabolism; Calcium Channels - genetics; Calcium Channels - metabolism; Cell Movement - genetics; Cells, Cultured; Cellular Biology; Gastrula - embryology; Gastrulation - genetics; Gene Knockdown Techniques; Green Fluorescent Proteins - genetics; HeLa Cells; Humanities and Social Sciences; Humans; Life Sciences; Mice; Mitochondria - metabolism; Molecular Sequence Data; Morphogenesis; Morpholinos - genetics; multidisciplinary; Notochord - metabolism; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Science; Science (multidisciplinary); Sequence Alignment; Sequence Analysis, DNA; Voltage-Dependent Anion Channel 1 - genetics; Voltage-Dependent Anion Channel 1 - metabolism; Zebrafish - embryology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms3330

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. Ca 2+ is an intracellular messenger that has a critical role in zebrafish development. Here Prudent et al . show that during gastrulation, the newly identified Bcl-2 homologue, Bcl-wav and the mitochondrial calcium uniporter regulate cell migration by controlling mitochondrial Ca 2+ storage.