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

Abstract

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 antiapoptotic 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.

Epithelial-Mesenchymal Transition: A Groundless Skyscraper

“…Expression of other genes were detected in Xenopus embryos. Expression patterns of cdh1, cdh2, vim, snai1, sox2, cdk1, plk1, birc5, ezh2, lsd1, akt1 and ptk2 were from Zhang et al ( 2017) (Zhang et al, 2017); sox9 was from Lee and Saint-Jeannet (2011) (Lee and Saint-Jeannet, 2011); mcl1 from Sena et al (2020) (Sena et al, 2020); h2ax from Lee et al (2010) (Lee et al, 2010); src from Lewis et al (2017) (Lewis et al, 2017); and snai2 and twist1 were from Wang et al (2015) (Wang et al, 2015). Dorsal view is shown for Xenopus embryos, with the anterior of embryos to the left.…”

T-Cell Factors as Transcriptional Inhibitors: Activities and Regulations in Vertebrate Head Development

“…In this context, Caspase-3 acts either in parallel, or downstream of Barhl2, and its activity does not depend on its apoptosis-effector function. In addition, in the neuroepithelium, Caspase-7 acts as the executioner Caspase leading to cell death ( Sena et al, 2020 ). Indeed, how Barhl2 regulates Caspase-3 non-apoptotic activity in Xenopus and limits β-catenin levels and stability in the developing diencephalon is unknown.…”