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Epithelial Geometry Regulates Spindle Orientation and Progenitor Fate During Formation of the Mammalian Epidermis

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서명/저자사항Epithelial Geometry Regulates Spindle Orientation and Progenitor Fate During Formation of the Mammalian Epidermis.
개인저자Box, Kimberly Simone.
단체저자명Princeton University. Molecular Biology.
발행사항[S.l.]: Princeton University., 2019.
발행사항Ann Arbor: ProQuest Dissertations & Theses, 2019.
형태사항94 p.
기본자료 저록Dissertations Abstracts International 81-04B.
Dissertation Abstract International
ISBN9781085772594
학위논문주기Thesis (Ph.D.)--Princeton University, 2019.
일반주기 Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Advisor: Devenport, Danelle.
이용제한사항This item must not be sold to any third party vendors.This item must not be added to any third party search indexes.
요약The ability to control cell fate through oriented division is imperative for the proper development of many organs, such as the stratified epidermis. Basal progenitor cells of the mammalian epidermis orient their divisions parallel or perpendicular to the basement membrane to expand the stem cell pool or produce differentiated stratified layers. Although any given basal cell is capable of either division orientation, the mechanisms that regulate the choice between division orientations are unknown. Here, using time-lapse imaging to follow divisions and fates of basal progenitors, we investigate the role of planar cell polarity (PCP) and tissue architecture during epidermal stratification. We find that embryos defective for the core PCP gene, Vangl2, exhibit increased perpendicular, asymmetric divisions at the expense of planar, symmetric divisions, but surprisingly, this is not due to defective Vangl2 function in the epidermis. We link this reduction in planar divisions to alterations in cell geometry and packing, which are indirectly caused by the neural tube closure defects characteristic of planar cell polarity mutants. We demonstrate that early in epidermal stratification, there is a close relationship between cell density, interphase cell height-to-width aspect ratio, and mitotic spindle orientation. These data show that basal epidermal cells utilize packing and shape, rather than cortical PCP cues, to inform division orientation. We propose a model in which local tissue architecture regulates the decision between symmetric and stratifying divisions, a mechanism that allows flexibility for basal stem cells to adapt to the needs of the developing tissue.
일반주제명Molecular biology.
Developmental biology.
Cellular biology.
Physiology.
Histology.
Health sciences.
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