Molecular Embryogenesis of the Visual System
University of Cambridge
Where does the nervous system come from in the embryo? How does it grow to the right size and shape? How do stem cells turn into more committed neuronal progenitors and how do these cells know when to leave the cycle and differentiate into neural and glial progenitors? How do particular regions of the nervous system produce the right number of neurons and the right proportions of the different types of neurons? Once born, how do these precursors differentiate? How do they choose a particular cell type to become amongst a myriad of possible fates, and by what cellular mechanisms do these cells become properly polarised, branched, and integrated into the retinal circuitry? What mechanisms allow retinal ganglion cells to send out long axons that forge pathways to their targets in the brain, and recognise specific cells within these targets? The visual systems of Xenopus and zebrafish are ideal for such questions because of their embryological, molecular and genetic accessibility to experimentation, combined with the possibility of in vivo time-lapse imaging. The retina is an excellent system to explore the issue of cellular proliferation and diversity. We are unravelling some of the lineage dependent and lineage independent events that are used to push or induce cells to transition from proliferating retinal stem cells to differentiated neurons and glia particular fates and testing a variety of hypotheses concerning the mechanisms of fate specification and histogenesis. We are using similar approaches to investigate the mechanisms involved in the initial morphogenesis of various retinal neuron types. We are also conducting a variety of experiments on how the growing axons gather and transduce the information that allows them to find their way to their targets, exploring the machinery and the dynamics of growth cones at a molecular level. The generation of the various components and the interconnections of the brain is the general problem towards which research in this lab is directed. How a functioning brain is built out of sheet of uncommitted pluripotential ectodermal cells is addressed by focusing on the developing visual systems of lower vertebrates and breaking the problem down into discrete developmental events such as cell fate determination and axonal navigation. We use various molecular and imaging tools to dissect these events.