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

Rodrigo A P Martins, Frederique Zindy, Stacy Donovan, Jiakun Zhang, Stanley Pounds, Alice Wey, Paul S Knoepfler, Robert N. Eisenman, Martine F. Roussel, Michael A. Dyer

Research output: Contribution to journalArticle

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)179-193
Number of pages15
JournalGenes and Development
Volume22
Issue number2
DOIs
StatePublished - Jan 15 2008

Keywords

  • Cell cycle
  • Cyclin D1
  • p27Kip1
  • Proliferation
  • Proto-oncogene

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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  • Cite this

    Martins, R. A. P., Zindy, F., Donovan, S., Zhang, J., Pounds, S., Wey, A., Knoepfler, P. S., Eisenman, R. N., Roussel, M. F., & Dyer, M. A. (2008). N-myc coordinates retinal growth with eye size during mouse development. Genes and Development, 22(2), 179-193. https://doi.org/10.1101/gad.1608008