N-myc coordinates retinal growth with eye size during mouse development.
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.
Martins
Rodrigo A P
RA
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Zindy
Frederique
F
Donovan
Stacy
S
Zhang
Jiakun
J
Pounds
Stanley
S
Wey
Alice
A
Knoepfler
Paul S
PS
Eisenman
Robert N
RN
Roussel
Martine F
MF
Dyer
Michael A
MA
D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D005123:Eye / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D016259:Genes, myc; D051379:Mice; D012160:Retina / Q000196:embryology*; D013234:Stem Cells / Q000502:physiology
C493961:Cdkn1b protein, mouse; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27