St. Jude defines eye cancer gene's role in retinal development

In the course of their study, the researchers discovered that N-myc is not involved in regulating cell survival or neuronal differentiation in the developing retina. However, the gene is crucial for the proper proliferation of retinal cells. In mice in which the scientists inactivated N-myc, the volume of the retina was significantly smaller than in mice with normally functioning N-myc.

The team found no evidence of an increase in progenitor cell deaths between normal and N-myc-deficient retinas. The investigators then concluded the smaller retinas likely resulted from an N-myc-related proliferation defect in the progenitor retinal cells.

The researchers hypothesize that N-myc’s activity occurs early in the cascade of reactions that control development of the retina and other eye components. Therefore, when something inactivates the gene, the result is both a reduction in retinal progenitor cell proliferation and a reduction in the signaling cues that coordinate the growth of the eye and retina.

“Importantly, for retinas to maintain nearly constant thickness across species that have different sizes of eyes, the total number of retinal cells must change several-fold,” Dyer said. “The identification of N-myc as a key regulator of these processes allows us to begin to understand the coordination of complex developmental programs in the developing eye and how these processes have evolved.”

Other authors of this paper include Rodrigo A.P. Martins, Frederique Zindy, Stacy Donovan, Jiakun Zhang, Stanley Pounds and Martine F. Roussel (St. Jude); Alice Wey and Paul S. Knoepfler (University of California at Davis and Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, Calif.); and Robert N. Eisenman (Fred Hutchinson Cancer Research Center, Seattle).

This work was supported by grants from the National Institutes of Health, Cancer Center Support from the National Cancer Institute, Research to Prevent Blindness, the American Cancer Society, the Pearle Vision Foundation and ALSAC. Dyer is a Pew Scholar.

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit www.stjude.org.