Robust control of mitotic spindle orientation in the developing epidermis

J Cell Biol. 2010 Nov 29;191(5):915-22. doi: 10.1083/jcb.201008001. Epub 2010 Nov 22.

Abstract

Progenitor cells must balance self-amplification and production of differentiated progeny during development and homeostasis. In the epidermis, progenitors divide symmetrically to increase surface area and asymmetrically to promote stratification. In this study, we show that individual epidermal cells can undergo both types of division, and therefore, the balance is provided by the sum of individual cells' choices. In addition, we define two control points for determining a cell's mode of division. First is the expression of the mouse Inscuteable gene, which is sufficient to drive asymmetric cell division (ACD). However, there is robust control of division orientation as excessive ACDs are prevented by a change in the localization of NuMA, an effector of spindle orientation. Finally, we show that p63, a transcriptional regulator of stratification, does not control either of these processes. These data have uncovered two important regulatory points controlling ACD in the epidermis and allow a framework for analysis of how external cues control this important choice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins
  • Cell Differentiation
  • Cell Division
  • Epidermal Cells
  • Epidermis / metabolism
  • Epidermis / ultrastructure*
  • Fluorescent Antibody Technique
  • Mice
  • Nuclear Proteins / analysis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphoproteins / metabolism
  • Spindle Apparatus / metabolism
  • Spindle Apparatus / ultrastructure*
  • Stem Cells / cytology
  • Stem Cells / metabolism

Substances

  • Cell Cycle Proteins
  • Nuclear Proteins
  • Numa1 protein, mouse
  • Phosphoproteins