Differential CRX and OTX2 expression in human retina and retinoblastoma
Article first published online: 3 AUG 2009
© 2009 The Authors. Journal Compilation © 2009 International Society for Neurochemistry
Journal of Neurochemistry
Volume 111, Issue 1, pages 250–263, October 2009
How to Cite
Glubrecht, D. D., Kim, J.-H., Russell, L., Bamforth, J. S. and Godbout, R. (2009), Differential CRX and OTX2 expression in human retina and retinoblastoma. Journal of Neurochemistry, 111: 250–263. doi: 10.1111/j.1471-4159.2009.06322.x
- Issue published online: 14 SEP 2009
- Article first published online: 3 AUG 2009
- Received June 22, 2009; revised manuscript received July 13, 2009; accepted July 29, 2009.
- cone-rod homeobox;
- orthodenticle homeobox 2;
The histogenesis of retinoblastoma tumors remains controversial, with the cell-of-origin variably proposed to be an uncommitted retinal progenitor cell, a bipotent committed cell, or a cell committed to a specific lineage. Here, we examine the expression of two members of the orthodenticle family implicated in photoreceptor and bipolar cell differentiation, cone-rod homeobox, CRX, and orthodenticle homeobox 2, OTX2, in normal human retina, retinoblastoma cell lines and retinoblastoma tumors. We show that CRX and OTX2 have distinct expression profiles in the developing human retina, with CRX first expressed in proliferating cells and cells committed to the bipolar lineage, and OTX2 first appearing in the photoreceptor lineage. In the mature retina, CRX levels are highest in photoreceptor cells whereas OTX2 is preferentially found in bipolar cells and in the retinal pigmented epithelium. Both CRX and OTX2 are widely expressed in retinoblastoma cell lines and in retinoblastoma tumors, although CRX is more abundant than OTX2 in the differentiated elements of retinoblastoma tumors such as large rosettes, Flexner-Wintersteiner rosettes and fleurettes. Widespread expression of CRX and OTX2 in retinoblastoma tumors and cell lines suggests a close link between the cell-of-origin of retinoblastoma tumors and cells expressing CRX and OTX2.