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Distinct patterns of expression of the RB gene family in mouse and human retina
Clarellen Spencer1, Sanja Pajovic, Hollie Devlin
1The Division of Cancer Informatics, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, Toronto, Canada.
Abstract:
Although RB1 function is disrupted in the majority of human cancers, an undefined cell of developing human retina is uniquely sensitive to cancer induction when the RB1 tumor suppressor gene is lost. Murine retinoblastoma is initiated only when two of the RB family of genes, RB1 and p107 or p130, are inactivated. Although whole embryonic retina shows RB family gene expression by several techniques, when E14 developing retina was depleted of the earliest differentiating cells, ganglion cells, the remaining proliferating murine embryonic retinal progenitor cells clearly did not express RB1 or p130, while the longer splice form of p107 was expressed. Each retinal cell type expressed some member of the RB family at some stage of differentiation. Rod photoreceptors stained for the RB1 protein product, pRB, and p107 in only a brief window of postnatal murine development, with no detectable staining for any of the RB family proteins in adult human and mouse rod photoreceptors. Adult mouse and human Muller glia, ganglion and rare horizontal cells, and adult human, but not adult mouse, cone photoreceptors stained for pRB. The RB gene family is dynamically and variably expressed through retinal development in specific retinal cells.
Insights
The Retinoblastoma (RB) gene family is crucial for preventing cancer. Specific retinal cells show unique sensitivity to RB1 gene loss, with dynamic expression patterns during development.
Area of Science:
- Ophthalmology
- Molecular Biology
- Oncology
Background:
- The Retinoblastoma (RB) gene (RB1) is a tumor suppressor frequently disrupted in human cancers.
- Developing human retina exhibits unique sensitivity to RB1 loss, leading to cancer induction.
- Murine retinoblastoma requires inactivation of RB1 and either p107 or p130.
Purpose of the Study:
- To investigate the expression patterns of the RB gene family during murine retinal development.
- To identify specific retinal cell types and developmental stages sensitive to RB gene family alterations.
Main Methods:
- Analysis of RB gene family expression in developing murine retina using various techniques.
- Depletion of specific cell types (ganglion cells) from embryonic retina to study progenitor cell expression.
- Immunohistochemical staining for RB family proteins (pRB, p107) in different retinal cell types across developmental stages.
Main Results:
- Proliferating murine embryonic retinal progenitor cells, after ganglion cell depletion, expressed p107 but not RB1 or p130.
- Rod photoreceptors transiently expressed pRB and p107 during early postnatal development, with no expression in adults.
- Adult Muller glia, ganglion cells, horizontal cells, and human cone photoreceptors expressed pRB, demonstrating dynamic and cell-type-specific expression.
Conclusions:
- The RB gene family exhibits dynamic and variable expression across different retinal cell types and developmental stages.
- Understanding these expression patterns is crucial for comprehending retinal development and cancer susceptibility related to RB gene function.
