Format

Send to

Choose Destination
Elife. 2016 Jan 14;5. pii: e12504. doi: 10.7554/eLife.12504.

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

Author information

1
Department of Dermatology, Duke University Medical Center, Durham, United States.
2
Department of Cell Biology, Duke University Medical Center, Durham, United States.

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.

KEYWORDS:

NuMA; asymmetric cell division; cell biology; developmental biology; mouse; skin; spindle orientation; stem cells

PMID:
26765568
PMCID:
PMC4758947
DOI:
10.7554/eLife.12504
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center