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Tight junction protein occludin regulates progenitor Self-Renewal and survival in developing cortex.

07:00 EST 3rd December 2019 | BioPortfolio

Summary of "Tight junction protein occludin regulates progenitor Self-Renewal and survival in developing cortex."

() mutations cause human microcephaly and cortical malformation. A tight junction component thought absent in neuroepithelium after neural tube closure, OCLN isoform-specific expression extends into corticogenesis. Full-length and truncated isoforms localize to neuroprogenitor centrosomes, but full-length OCLN transiently localizes to plasma membranes while only truncated OCLN continues at centrosomes throughout neurogenesis. Mimicking human mutations, full-length OCLN depletion in mouse and in human CRISPR/Cas9-edited organoids produce early neuronal differentiation, reduced progenitor self-renewal and increased apoptosis. Human neural progenitors were more severely affected, especially outer radial glial cells, which mouse embryonic cortex lacks. Rodent and human mutant progenitors displayed reduced proliferation and prolonged M-phase. OCLN interacted with mitotic spindle regulators, NuMA and RAN, while full-length OCLN loss impaired spindle pole morphology, astral and mitotic microtubule integrity. Thus, early corticogenesis requires full-length OCLN to regulate centrosome organization and dynamics, revealing a novel role for this tight junction protein in early brain development.

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This article was published in the following journal.

Name: eLife
ISSN: 2050-084X
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Medical and Biotech [MESH] Definitions

A MARVEL domain protein that binds to and regulates PROTEIN PHOSPHATASE 1. Occludin plays an important role in the formation and regulation of the TIGHT JUNCTION paracellular permeability barrier.

Proteins that take part in the formation or structure of TIGHT JUNCTIONS.

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The ability of certain cell types, such as progenitor cells or tumor cells, to go through numerous cycles of CELL DIVISION while still maintaining an undifferentiated or partially differentiated state.

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