home | research | publications | lab members | links | contact

Areas of Research: Basic helix-loop-helix (bHLH) transcription factors and retinal neurogenesis Wnt/Frizzled signaling during vertebrate eye development Glaucoma - a progressive loss of retinal ganglion cells bHLH factors and retinal neurogenesis: Basic-helix-loop-helix (bHLH) transcription factors are important regulators of neuronal differentiation. We have identified a bHLH gene, Xath5, which regulates neurogenesis in the retina, and is specifically involved in the development of retinal ganglion cells. To understand how bHLH factors regulate retinal neuron differentiation we have been investigating how various negative regulatory pathways modulate the function of bHLH factors during retinogenesis. We have found that both the Notch pathway and components of the wnt/frizzled signaling pathway can modulate the timing of bHLH factor function during retinal development. Furthermore, we find that this regulation is critical for controlling the timing of retinal neuron differentiation. To further explore how bHLH factors regulate the differentiation of retinal precursor cells, we are identifying transcriptional target genes whose expression is dependent upon the function of bHLH proteins, and which may be involved in subsequent stages of neuronal differentiation. In addition, we are using transgenic approaches in Xenopus embryos to identify the signals that initiate the expression of eye-specific genes during retinal development as a basis for understanding the sequence of events leading to normal nervous system development. Wnt/Frizzled signaling and vertebrate eye development: To understand how extrinsic signaling pathways regulate different stages of eye development, we are examining the role of wnt signaling. Wnt ligands bind to members of the frizzled family of transmembrane receptors. Recently, we have found that frizzled receptors can regulate several aspects of eye development. We are currently investigating how frizzled receptors and downstream signaling components are involved in regulating proliferation and differentiation in the developing eye using both mouse and Xenopus as model systems. Glaucoma causes blindness due to a progressive loss of retinal ganglion cells: Glaucoma is a devastating disease that causes blindness due to a progressive loss of retinal ganglion cells. In many, but not all cases this is due to an increase in intraocular pressure that triggers retinal ganglion cell death. Little is known about the molecular mechanisms underlying glaucoma progression. We are participating in a collaborative research consortium called Catalyst for a Cure that is funded by the Glaucoma Research Foundation and the Steven and Michele Kirsch Foundation. We are collaborating with investigators at the University of Washington, Seattle, Johns Hopkins University and University of Rochester to apply molecular and genetic tools to better understand the pathogenesis of glaucoma. In particular we are using microarray techniques to profile changes in gene expression during disease progression in a mouse model of glaucoma. home | research | publications | lab members | links | contact