Bcl-2 proteins, cell migration and embryonic development: lessons from zebrafish
Bibliographic record
Abstract
B-cell lymphoma-2 ( Bcl-2 ) was cloned 30 years ago and associated with B-cell follicular lymphoma. A number of Bcl-2 homologs were identified later on. Importantly, the Bcl-2 family was found to control the mitochondrial outer membrane permeabilization: a key step of the mitochondrial pathway of apoptosis. 1 Bcl-2 homologs are evolutionarily conserved throughout metazoans and considered as the hallmarks of multicellularity. Genetic manipulation in nematodes and mice demonstrated that the bcl-2 family has a pivotal role in tissue homeostasis by controlling cell death; however, an increased number of in vitro studies have identified additional non-apoptotic functions, suggesting that Bcl-2 proteins are in fact multitask factors ( Figure 1a ). 2 Figure 1 Non-apoptotic functions of the Bcl-2 family of proteins. ( a ) Simplified representation of Bcl-2 proteins functions. Bcl-2 proteins are multitask factors and linked to non-apoptotic functions. The top panel represents the different Ca 2+ -independent functions linked to the Bcl-2 family of proteins, whereas the bottom panel highlights roles that may be attributed to Bcl-2 proteins, thanks to their capacity to regulate intracellular Ca 2+ homeostasis (reviewed in Bonneau et al. 2 ). ( b ) Nrz and Bcl-wav regulate cell migration and zebrafish embryonic development by the control of intracellular Ca 2+ fluxes via their interactions with IP 3 R and VDAC1, respectively. Invalidation of either nrz or bclwav leads to an increase of cytosolic Ca 2+ level inside the embryo inducing cytoskeleton defects. These two proteins are involved in crucial morphogenetic movements, which occur during gastrulation, whereas, surprisingly, they do not appear to be involved in apoptosis control at that stage. Interaction of Nrz with IP 3 R is regulated by Nrz phosphorylation, which disrupts Nrz/IP 3 R interaction and leads to ER-Ca 2+ release. Nrz can also be localized to mitochondria where it prevents apoptosis. 7 This function is not described here as it is not related to cell migration and appears to be important only at later stages of zebrafish development. Only the interacting partners of the Bcl-2 family of proteins directly involved in the regulation of Ca 2+ trafficking are represented. ( c ) Scheme of the dorsal view of zebrafish (7 h post fertilization) and mouse (6.5 days post fertilization) gastrulae. During early zebrafish development, cells migrate towards the vegetal pole in a movement called epiboly (dark red arrows). At 50% epiboly, at the dorsal side, cells start invaginating (purple arrows). Notochord precursor cells migrate actively towards the dorsal and the anterior–posterior poles in a movement called convergence-extension (CE; green arrows). In comparison, the mouse embryo does not show epiboly morphogenesis. CE movements are much smaller, compared with zebrafish. AP: animal pole; VP: vegetal pole Full size image
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".