title: N-myc coordinates retinal growth with eye size during mouse development.
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.
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Rodrigo A P
authors.initials: RA
authors.lastname: Martins
authors.forename: Frederique
authors.initials: F
authors.lastname: Zindy
authors.forename: Stacy
authors.initials: S
authors.lastname: Donovan
authors.forename: Jiakun
authors.initials: J
authors.lastname: Zhang
authors.forename: Stanley
authors.initials: S
authors.lastname: Pounds
authors.forename: Alice
authors.initials: A
authors.lastname: Wey
authors.forename: Paul S
authors.initials: PS
authors.lastname: Knoepfler
authors.forename: Robert N
authors.initials: RN
authors.lastname: Eisenman
authors.forename: Martine F
authors.initials: MF
authors.lastname: Roussel
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dyer
mesh_terms: 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
chemical_list: C493961:Cdkn1b protein, mouse; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27