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

• Type of Material: Article
• Authors: Lindsey Seldin, Emory University; Andrew Muroyama, Duke University; Terry Lechler, Duke University
• Language: English
• Date: 2016-01-14
• Publisher: ELIFE SCIENCES PUBLICATIONS LTD
• Publication Version: Final Published Version
• Copyright Statement: © 2016, Seldin et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.7554/eLife.12504
• Title of Journal or Parent Work: ELIFE
• Volume: 5
• Issue: JANUARY2016
• Start Page: e12504
• End Page: e12504
• Grant/Funding Information: This work was supported by NIH grants R01AR055926 and R01GM111336 to TL, and by a predoctoral fellowship to AM from NSF.
• Keywords: STEM-CELLS; TUBULIN; CAENORHABDITIS-ELEGANS; PROTEIN; Science & Technology; Life Sciences & Biomedicine; DROSOPHILA; CORTICAL DYNEIN; HAIR-FOLLICLE; ASYMMETRIC CELL DIVISIONS; C-ELEGANS; Biology; MITOTIC SPINDLE; Life Sciences & Biomedicine - Other Topics
• Research Categories: Biology, Cell

Abstract

Mitotic spindle orientation is used to generate cell fate diversity and drive proper tissue morphogenesis. A complex of NuMA and dynein/dynactin is required for robust spindle orientation in a number of cell types. Previous research proposed that cortical dynein/dynactin was sufficient to generate forces on astral microtubules (MTs) to orient the spindle, with NuMA acting as a passive tether. In this study, we demonstrate that dynein/dynactin is insufficient for spindle orientation establishment in keratinocytes and that NuMA’s MT-binding domain, which targets MT tips, is also required. Loss of NuMA-MT interactions in skin caused defects in spindle orientation and epidermal differentiation, leading to neonatal lethality. In addition, we show that NuMA-MT interactions are also required in adult mice for hair follicle morphogenesis and spindle orientation within the transit-amplifying cells of the matrix. Loss of spindle orientation in matrix cells results 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.