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

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Division*
  • Dynactin Complex / metabolism
  • Dyneins / metabolism
  • Keratinocytes / physiology*
  • Mice
  • Microtubules / metabolism
  • Morphogenesis
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Skin Physiological Phenomena
  • Spindle Apparatus / metabolism*

Substances

  • Dynactin Complex
  • Nuclear Proteins
  • Numa1 protein, mouse
  • Dyneins