Developmental cell death of cortical projection neurons is controlled by a Bcl11a/Bcl6-dependent pathway.

Autor: Wiegreffe C; Institute of Molecular and Cellular Anatomy, Ulm University, Ulm, Germany., Wahl T; Institute of Molecular and Cellular Anatomy, Ulm University, Ulm, Germany., Joos NS; Institute of Molecular and Cellular Anatomy, Ulm University, Ulm, Germany., Bonnefont J; Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), Brussels, Belgium.; VIB-KU Leuven Center for Brain & Disease Research, KU Leuven Department of Neuroscience, Leuven Brain Institute, Leuven, Belgium., Liu P; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Britsch S; Institute of Molecular and Cellular Anatomy, Ulm University, Ulm, Germany.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2022 Aug 03; Vol. 23 (8), pp. e54104. Date of Electronic Publication: 2022 Jun 29.
DOI: 10.15252/embr.202154104
Abstrakt: Developmental neuron death plays a pivotal role in refining organization and wiring during neocortex formation. Aberrant regulation of this process results in neurodevelopmental disorders including impaired learning and memory. Underlying molecular pathways are incompletely determined. Loss of Bcl11a in cortical projection neurons induces pronounced cell death in upper-layer cortical projection neurons during postnatal corticogenesis. We use this genetic model to explore genetic mechanisms by which developmental neuron death is controlled. Unexpectedly, we find Bcl6, previously shown to be involved in the transition of cortical neurons from progenitor to postmitotic differentiation state to provide a major checkpoint regulating neuron survival during late cortical development. We show that Bcl11a is a direct transcriptional regulator of Bcl6. Deletion of Bcl6 exerts death of cortical projection neurons. In turn, reintroduction of Bcl6 into Bcl11a mutants prevents induction of cell death in these neurons. Together, our data identify a novel Bcl11a/Bcl6-dependent molecular pathway in regulation of developmental cell death during corticogenesis.
(© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
Databáze: MEDLINE
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