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Mcl1 protein levels and Caspase-7 executioner protease control axial organizer cells survival
Elena Sena1,2, Johnny Bou-Rouphael3, Nathalie Rocques1,2
1Institut Curie, PSL Research University, Orsay, France.
Background:
Organizing centers are groups of specialized cells that secrete morphogens, thereby influencing development of their neighboring territories. Apoptosis is a form of programmed cell death reported to limit the size of organizers. Little is known about the identity of intracellular signals driving organizer cell death. Here we investigated in Xenopus the role of both the anti-apoptotic protein Myeloid-cell-leukemia 1 (Mcl1) and the cysteine proteases Caspase-3 and Caspase-7 in formation of the axial organizing center-the notochord-that derives from the Spemann organizer, and participates in the induction and patterning of the neuroepithelium.
Results:
We confirm a role for apoptosis in establishing the axial organizer in early neurula. We show that the expression pattern of mcl1 is coherent with a role for this gene in early notochord development. Using loss of function approaches, we demonstrate that Mcl1 depletion decreases neuroepithelium width and increases notochord cells apoptosis, a process that relies on Caspase-7, and not on Caspase-3, activity. Our data provide evidence that Mcl1 protein levels physiologically control notochord cells' survival and that Caspase-7 is the executioner protease in this developmental process.
Conclusions:
Our study reveals new functions for Mcl1 and Caspase-7 in formation of the axial signalling center.
Insights
Myeloid-cell-leukemia 1 (Mcl1) and Caspase-7 control cell death in the developing notochord, a key axial organizer. This research clarifies their roles in early vertebrate development.
Area of Science:
- Developmental Biology
- Cell Biology
- Molecular Biology
Background:
- Organizing centers are crucial for embryonic development, secreting morphogens that guide tissue formation.
- Programmed cell death (apoptosis) is known to regulate organizer size, but the underlying molecular mechanisms are unclear.
- This study focuses on the roles of Myeloid-cell-leukemia 1 (Mcl1) and Caspase-3/7 in axial organizer development.
Purpose of the Study:
- To investigate the function of the anti-apoptotic protein Mcl1 and executioner caspases (Caspase-3 and Caspase-7) in the formation of the Xenopus notochord.
- To elucidate the intracellular signaling pathways governing cell death within the Spemann organizer derivatives.
Main Methods:
- Utilized Xenopus laevis model system for studying early vertebrate development.
- Employed loss-of-function approaches to deplete Mcl1 expression.
- Analyzed the impact of Mcl1 depletion on notochord cell apoptosis and neuroepithelium development.
Main Results:
- Confirmed the role of apoptosis in establishing the axial organizer during early neurulation.
- Demonstrated that Mcl1 expression patterns align with its function in notochord development.
- Showed that Mcl1 depletion leads to increased notochord cell apoptosis mediated by Caspase-7, not Caspase-3, and reduces neuroepithelium width.
Conclusions:
- Mcl1 protein levels are critical for regulating notochord cell survival during development.
- Caspase-7 acts as the primary executioner protease in Mcl1-dependent apoptosis within the notochord.
- Identified novel functions for Mcl1 and Caspase-7 in the formation of the axial signaling center.
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