Research Interests

    The overall objectives of current research efforts in the Raymond laboratory are to understand the molecular basis of cell-cell interactions that regulate retinal neurogenesis (the formation and regeneration of neurons) and neuronal specificity (the expression of differentiated cellular features), and to define and characterize the molecular profiles of retinal stem cells and retinal progenitor cells in the embryonic and adult zebrafish retina. We are characterizing the cellular and molecular properties of retinal stem cells and progenitors, and we are seeking to understand the regulatory mechanisms that control proliferation, determination, differentiation and patterning of retinal neurons, especially photoreceptors. Because of the strong evolutionary conservation of structure and function in the vertebrate retina, the cellular and molecular properties of the teleost fish retina are remarkably similar to those of the mammalian retina, and we believe that studying stem cells in the fish retina, which are able to effectively repair and regenerate the neural retina even in the adult, will help us to uncover fundamental and universal properties of neural stem cells in humans.

    In collaboration with several other laboratories, we have recently cloned and characterized several zebrafish genes that encode homeodomain transcription factors involved in specification of eyes and the determination and differentiation of retinal cells, including the retinal homeobox, Rx, and the cone-rod homeobox, Crx. Mutations in the human orthologues of both these genes have been implicated in congenital ocular/retinal disorders.

    We also recently demonstrated the phenotypic plasticity of Müller glial cells in response to retinal injury as an initial test of the hypothesis that they function as retinal stem cells. Since activation of the Notch signaling pathway has been shown to be gliogenic in zebrafish and mouse retinal progenitors, directing them to differentiate as glia instead of neurons, we are testing the hypothesis that Müller glia can function as retinal stem cells by developing constructs target activated Notch signaling specifically to differentiated Müller glia. We will then ask, can Müller glia with constitutively active Notch signaling participate in regeneration of retinal neurons? If retinal regeneration is blocked, this would be strong support for Müller glia as the source of retinal stem cells. In addition, we are examining zebrafish mutant lines that interfere with Notch signaling to ask, what is the retinal phenotype of these mutants? Is the number of Müller glia reduced? What is regeneration potential of the mutant retinas?

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The University of Michigan Department of Molecular, Cellular and Developmental Biology

Last modified 03/09/06