Prof. Dr. Joachim Wittbrodt
Vertebrate eye and brain development and regeneration
The vertebrate eye is composed of neuroectodermal (optic cup) and surface ectodermal (lens, cornea) derivatives and it emerges from an epithelial Anlage by inductive interactions beginning al late gastrula stages. Under the influence of midline signaling during neurulation the single retina Anlage is split into two retinal primordia localized in the lateral wall of the forebrain.
Subsequent evagination of the primordia results in the formation of optic vesicles that differentiate to the seven cell types of the neural retina, the retinal pigmented epithelium and the optic stalk respectively. In anamniotes (fish, amphibia), the ciliary marginal zone (CMZ) of the neural retina contains a stem cell population that gives rise to all retinal cell types and facilitates life-long growth of the eye.
The lab is studying neuronal cell proliferation and differentiation in the developing, growing and regenerating eye and brain of fish (zebrafish, medaka) as model system. We are combining genetic, molecular and cell biological approaches with advanced imaging approaches to decipher the basic mechanisms that govern the balance of cell proliferation and differentiation in vivo. Special emphasis is given to follow the fate of proliferating and differentiating cells in the context of the fish retina and brain and to establish tools that allow visualizing the those processes in vivo. We take advantage of the life-long proliferation of retinal stem cells from the ciliary marginal zone (CMZ) that facilitates the continuous study of cells exiting the stem cell niche at the CMZ and their subsequent stereotypic differentiation. These processes can be functionally addressed by mutants established in a collaborative mutagenesis screen or available in the community. Novel tools developed in the lab allow to perform clonal analysis in 4D by the induction of the expression of genes of interest at physiological levels in individual retinal cells of any cell type. The combination of these approaches with the systematic analysis of transcription factors that control the expression of key genes will contribute to a functional understanding of the molecular processes that govern the proliferation and differentiation of retinal stem cells. In an evolutionary context these approaches will also address the specific features of retinal stem cells in fish that have not been retained in mammals.
With all the functional and visualization tools developed so far we have started going the next step towards functionally analyzing neuronal networks within the retina and beyond.
Future research goals
Systematic approaches to identify the key transcription factors that trigger and maintain retinal neurons in their differentiated state
Systematic analysis of gene expression, regulatory input and modulation
Decipher the regulatory logic of retinal stem cell proliferation and terminal differentiation
Digital retina, Multidimensional database incorporating all the experimental data available that allows to directly derive hypotheses