Mcl1 protein levels and Caspase‐7 executioner protease control axial organizer cells survival

• Published in: Developmental dynamics Vol. 249; no. 7; pp. 847 - 866
• Main Authors: Sena, Elena, Bou‐Rouphael, Johnny, Rocques, Nathalie, Carron‐Homo, Clémence, Durand, Béatrice C.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-07-2020; Wiley Subscription Services, Inc; Wiley
• Subjects: Apoptosis; Caspase; Cell Behavior; Cell death; Cellular Biology; Depletion; Development Biology; Embryology and Organogenesis; Leukemia; Life Sciences; Mcl-1 protein; mcl1; Morphogenesis; neuroepithelium; Notochord; organizer; Pattern formation; Patterning; Protease; Proteins; Subcellular Processes; Survival; xenopus; mcl1; apoptosis; neuroepithelium; organizer; xenopus
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.169

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.