A key mechanism regulating neural stem cell development is uncovered



    MONTREAL, Oct. 8 /CNW Telbec/ - A research team at the Institut de
recherches cliniques de Montreal (IRCM), funded by the Foundation Fighting
Blindness - Canada and the Canadian Institutes of Health Research (CIHR),
discovered a novel mechanism that regulates how neural stem cells of the
retina generate the appropriate cell type at the right time during normal
development. These findings, published today in the renowned journal Neuron,
could influence the development of future cell replacement therapies for
genetic eye diseases that cause blindness.
    In their report, the scientists show that a gene called Ikaros is
expressed in the most immature retinal stem cells in the mouse, which are
"competent" to generate all seven different cell types that compose the
retina. But this gene is not expressed in the "older" stem cells, which are
more restricted in their differentiation potential and produce only the
late-born neurons. "By studying the retina of a mouse in which the Ikaros gene
was inactivated, we found that the generation of early-born retinal cell types
was impaired, whereas the generation of the late-born retinal cell types was
not affected," explained Dr. Michel Cayouette who led the study. In contrast,
forcing the expression of Ikaros in older retinal stem cells, which have
normally turned off its expression, was sufficient to give back the competence
to these cells to generate early-born neurons. Overall, these results indicate
that the expression of Ikaros in retinal stem cells is both necessary and
sufficient to confer the competence to generate early-born retinal neurons.
    The identification of adult retinal stem cells in recent years has opened
up the possibility that such cells could one day be used to replace damaged or
lost cells in various retinal diseases such as glaucoma, macular degeneration
or retinitis pigmentosa. For such approaches to be effective, however, it is
crucial that stem cells generate only the appropriate cell type for a
particular condition. This study suggests that it may be possible to
manipulate the competence of retinal stem cells so that they only generate
retinal cells associated to a particular temporal stage. "For example, added
Dr. Cayouette, inactivating Ikaros could favor the production of later-born
neurons such as photoreceptors, which are lost progressively in retinal
degenerative diseases." Future studies will be required to assess the
usefulness of this approach for potential cell replacement therapies.

    Reference: Jimmy Elliott, Christine Jolicoeur, Vasanth Ramamurthy, and
Michel Cayouette. (2008) Ikaros confers early temporal competence to mouse
retinal progenitor cells. Neuron Volume 60 October 9, 2008, 26-39.

    Dr. Michel Cayouette is Director of the Cellular Neurobiology Research
Unit at the IRCM. Dr. Cayouette is also Associate Researcher at the Université
de Montréal. This research is supported by grants from the Foundation Fighting
Blindness - Canada and the Canadian Institutes of Health Research (CIHR).

    Established in 1967, the IRCM (www.ircm.qc.ca) now has 37 research units
specialized in areas as diversified as systems biology, immunity and viral
infections, cardiovascular and metabolic diseases, cancer, medicinal
chemistry, clinical research and ethical reflection. It has a staff of more
than 450. The IRCM is an independent institution, affiliated to Université de
Montréal. It has built over the years a close collaboration with McGill
University.




For further information:

For further information: Michel Cayouette, PhD, Director of the Cellular
Neurobiology Research Unit, (514) 987-5757, michel.cayouette@ircm.qc.ca,
www.ircm.qc.ca/microsites/cayouette/en; Lucette Thériault Communications
Director, (514) 987-5535, lucette.theriault@ircm.qc.ca, www.ircm.qc.ca

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Institut de recherches cliniques de Montréal (IRCM)

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