N-myc coordinates retinal growth with eye size during mouse development

Genes Dev. 2008 Jan 15;22(2):179-93. doi: 10.1101/gad.1608008.

Abstract

Myc family members play crucial roles in regulating cell proliferation, size, differentiation, and survival during development. We found that N-myc is expressed in retinal progenitor cells, where it regulates proliferation in a cell-autonomous manner. In addition, N-myc coordinates the growth of the retina and eye. Specifically, the retinas of N-myc-deficient mice are hypocellular but are precisely proportioned to the size of the eye. N-myc represses the expression of the cyclin-dependent kinase inhibitor p27Kip1 but acts independently of cyclin D1, the major D-type cyclin in the developing mouse retina. Acute inactivation of N-myc leads to increased expression of p27Kip1, and simultaneous inactivation of p27Kip1 and N-myc rescues the hypocellular phenotype in N-myc-deficient retinas. N-myc is not required for retinal cell fate specification, differentiation, or survival. These data represent the first example of a role for a Myc family member in retinal development and the first characterization of a mouse model in which the hypocellular retina is properly proportioned to the other ocular structures. We propose that N-myc lies upstream of the cell cycle machinery in the developing mouse retina and thus coordinates the growth of both the retina and eye through extrinsic cues.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Differentiation
  • Cell Proliferation
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Eye / embryology*
  • Gene Expression Regulation, Developmental
  • Genes, myc*
  • Mice
  • Retina / embryology*
  • Stem Cells / physiology

Substances

  • Cdkn1b protein, mouse
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27