Washington, Jan 17 : Working with mice, researchers at St. Jude Children's Research Hospital, have found that a gene called N-myc, coordinates the growth of the retina during foetal development, and that malfunctioning variants of this gene can also be linked to pediatric neural cancers like retinoblastoma.
The study led by Michael Dyer, Ph.D., associate member in the St. Jude Department of Developmental Neurobiology, also found that N-myc coordinates the growth of the retina and other eye structures to ensure that the retina has the proper thickness necessary to convert light from the lens into nerve impulses that the brain transforms into images.
"A series of complex developmental processes must be carefully orchestrated for the eye to form correctly. One important aspect of this coordination is that retinal thickness be the same, irrespective of eye size. For example, the mouse eye is about 5,000 times smaller than that of the elephant eye, but the retinal thickness in these two species is comparable," said Dyer.
He added: "This represents the first example of a role for a Myc gene in retinal development. On the basis of our data, we propose that N-myc plays a central role in coordinating retinal proliferation with eye growth during development."
Myc family genes perform vital roles during prenatal development by regulating the proliferation, size, differentiation and survival of cells. These genes are proto-oncogenes, which are genes in which a mutation enables them to transform normal cells into cancerous ones.
Malfunctioning N-myc genes are often associated with pediatric neural cancers, including neuroblastoma, medulloblastoma and retinoblastoma.
The researchers recently identified the specific type of cell that gives rise to retinoblastoma, a potentially fatal malignant tumor in the retina.
"The determination of N-myc target genes during retinal development may also contribute to the current understanding of retinoblastoma progression," said Dyer.
During the study, it was 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.
The volume of the retina was significantly smaller, in mice in which the scientists inactivated N-myc in comparison to mice with normally functioning N-myc.
No evidence of an increase in progenitor cell deaths was found between normal and N-myc-deficient retinas. This led the investigators to conclude that smaller retinas likely resulted from an N-myc-related proliferation defect in the progenitor retinal cells.
According to the researchers' hypothesis, N-myc's activity occurs early in the flow of reactions that control development of the retina and other eye components. Thus, in case of inactivation of the gene, it results in 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. 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," said Dyer.
The study is reported in the recent issue of "Genes and