The finding is important because it demonstrates that this single gene can perform two different functions during the embryonic retina development, according to Michael Dyer, Ph.D., an assistant member of the St. Jude Department of Developmental Neurobiology. Dyer is the lead author of a report on this work that appears in the May issue of Nature Genetics.
"The critical role we found for Prox1 in the retina supports a growing body of evidence we've been accumulating in the past few years indicating that Prox1 is a key player in orchestrating the proper development of the entire embryo," said Guillermo Oliver, Ph.D., an associate member of the St. Jude Department of Genetics and co-author of the paper.
Using a laboratory mouse model lacking the Prox1 gene, the researchers initially found that the gene was necessary for proper development of a layer of cells in the retina called horizontal cells. These cells process information sent by light-sensitive cells called rods. In the absence of Prox1, this layer was abnormally expanded with cells that had not become specialized into horizontal cells.
Researcher used a variety of techniques including radioactive tags to track newly produced DNA in dividing cells, DNA microarrays to identify differentially affected genes and specially engineered viruses to deliver Prox1 into retinal cells.
Results of these studies also showed that the control Prox1 exerts over the developing retina is so precise that it also ensures that there is one horizontal cell for every 150 rods.
"We found that Prox1 directs progenitor cells that will become the horizontal cells to stop multiplying so there will be only a limited number of these neurons," Dyer said. "So this study also helps to explain the big mystery of how horizontal cells succeed in making that critical ratio."
This latest discovery adds to the growing list of roles Prox1 plays. "Prox1 has been a central gene in every organ we've studied so far in the developing embryo," Oliver said. "We've previously discovered that Prox1 is critical to the normal development of the liver, the lens of the eye, and the entire lymphatic system, which is a critical part of the immune system."
The ongoing work at St. Jude has demonstrated that during embryo development, Prox1 plays at least three critical roles. It controls the proliferation of cells, prompts cells to migrate from their original positions in the embryo to the location where they will help form a tissue or organ and makes those cells become a very specialized cell type so they perform a specific task in that organ or tissue. Other authors of this report include Constance L. Cepko (Harvard University, Boston) and Frederick J. Livesey (Harvard University and Wellcome/CRC Institute of Cancer and Developmental Biology, University of Cambridge, UK).
This work received support from the National Institutes of Health, Charles H. Revson Fellowship for Biomedical Sciences, Cancer Center Support and ALSAC.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital, in Memphis, Tennessee, was founded by
the late entertainer Danny Thomas. The hospital is an internationally
recognized biomedical research center dedicated to finding cures for
catastrophic diseases of childhood. The hospital's work is supported through
funds raised by ALSAC. ALSAC covers all costs not covered by insurance for
medical treatment rendered at St. Jude Children's Research Hospital.
Families without insurance are never asked to pay. For more information,
please visit www.stjude.org.
Journal
Nature Genetics