Bcl-wav and the mitochondrial calcium uniporter drive gastrula morphogenesis in 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.
Université de Lyon, Centre de recherche en cancérologie de Lyon, U1052 INSERM, UMS 3453 CNRS, Université Lyon I, Centre Léon Bérard, 28 rue Laennec, Lyon 69008, France.
Julien
J
Prudent
Nikolay
N
Popgeorgiev
Benjamin
B
Bonneau
Julien
J
Thibaut
Rudy
R
Gadet
Jonathan
J
Lopez
Philippe
P
Gonzalo
Ruth
R
Rimokh
Stephen
S
Manon
Corinne
C
Houart
Philippe
P
Herbomel
Abdel
A
Aouacheria
Germain
G
Gillet
D000199:Actins / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001692:Biological Transport / Q000235:genetics; D001757:Blastomeres / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D005775:Gastrula / Q000196:embryology; D054262:Gastrulation / Q000235:genetics; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D009024:Morphogenesis; D060172:Morpholinos / Q000235:genetics; D009672:Notochord / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D050995:Voltage-Dependent Anion Channel 1 / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology*
D000199:Actins; D015220:Calcium Channels; D060172:Morpholinos; D019253:Proto-Oncogene Proteins c-bcl-2; C034703:mitochondrial calcium uniporter; D049452:Green Fluorescent Proteins; D050995:Voltage-Dependent Anion Channel 1; D002118:Calcium