NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures

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Abstract

Mitotic spindle orientation is used to generate cell fate diversity and tissue architecture. A complex of NuMA and dynein/dynactin is required for robust spindle orientation in a number of cell types. Previous research proposed that dynein/dynactin was sufficient to generate forces on microtubules (MTs) to orient spindles, with NuMA acting as a passive tether. In this study, we demonstrate that dynein/dynactin is insufficient for spindle orientation and that NuMA's MT-binding domain, which targets MT tips, is also required. Loss of NuMA-MT interactions caused defects in spindle orientation and epidermal differentiation, leading to neonatal lethality. We also show that loss of NuMA-MT interactions disrupts spindle orientation in the hair follicle matrix, resulting in defective differentiation of matrix-derived lineages. Our results reveal an additional and direct function of NuMA during mitotic spindle positioning, as well as a reiterative use of spindle orientation in the skin to build diverse structures.

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Lindsey Seldin

Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, United States

Competing interests
The authors declare that no competing interests exist.
Andrew Muroyama

Departments of Dermatology and Cell Biology, Duke University Medical Center, Durham, United States

Competing interests
The authors declare that no competing interests exist.
Terry Lechler

Departments of Dermatology and Cell Biology, Duke University Medical Center, Durham, United States

For correspondence
terry.lechler@duke.edu

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: All mouse studies were performed in accordance with our protocol (A147-15-05) approved by the Institutional Animal Care and Use Committee of Duke University (A147-15-05).

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.