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

Martins, Rodrigo A P and Zindy, Frederique and Donovan, Stacy and Zhang, Jiakun and Pounds, Stanley and Wey, Alice and Knoepfler, Paul S and Eisenman, Robert N and Roussel, Martine F and Dyer, Michael A (2008) N-myc coordinates retinal growth with eye size during mouse development. Genes & development, 22 (2). pp. 179-193. ISSN 0890-9369

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.

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