The mammalian retina and inner ear are two of the most common places of genetic diseases that cause blindness and deafness due to the degeneration of retinal and inner ear neurons. In order to understand the disease processes, it is very crucial to elucidate the fundamental mechanisms regulating the normal development and maintenance of these neurons at the molecular level. Our research is centered on identifying genes required for neuron differentiation and survival, investigating the genetic pathways involved in these processes, and developing therapies for blindness and deafness via gene therapy and stem cell replacement. We are currently investigating the roles of two classes of transcription factors in the development and survival of mouse retina and inner ear: (a) Math5 and Math1, the basic helix-loop-helix (bHLH) transcription factors homologous to Atonal, a Drosophila proneural transcription factor, and (b) Brn-3 factors, the Class IV POU-domain transcription factors. Using homologous recombination in murine embryonic stem (ES) cells to mutate math5 and brn-3 genes, we have show that the math-class genes regulate the differentiation of neuronal progenitor cells into specific types of neurons and that brn-3 genes are required for the maturation and survival of post-differentiation neurons.

Pub Med Citations

1.  Gan, L., Wang, S.W., Huang, Z., and Klein, W.H. (1999). Dev. Biol. 210, 469-480.

2. Wagner, D.S., Gan, L., and Klein, W.H. (1999). Biochem. Biophys. Res. Commun. 262, 677-684.

3. Wang, S.W., Gan, L., Martin, S.E., and Klein, W.H. (2000). Mol. Cell. Neurosci., 16, 141-156

4. Lu, J., Chang, P., Richardson, J.A., Gan, L., Weiler, H., Olson, E.N. (2000). Proc. Natl. Acad. Sci. USA. 97, 9525-9530.

5. Eng, S.R., Gratwick, K., Rhee, J.M., Fedtsova, N., Gan, L., and Turner, E.E. (2001). J. Neurosci. 21,  541-549.

6. Wang, S.W., Kim, B.S., Ding, K., Wang, H., Sun, D., Johnson, R.L, Klein, W.H. and Gan, L. (2001). Genes & Dev. 15, 24-29.

7. Kim, B.S., Savinova, O.V., Reedy, M.V., Martin, J., Lun, Y., Gan, L., Smith, R.S., Tomarev, S.I., John, S.W., and Johnson, R.L. (2001). Mol. Cell. Biol. 21, 7707-7713.

8. Mu, X., Zhao, S., Pershad, R., Tzung-Fu Hsieh, T-F., Scarpa, A., Wang, S.W., White, R.A., Thomas, T.L., Gan, L., and Klein, W.H. (2001). Nucleic Acids Res. 24, 4983-4993.

9. Wang, S.W., Mu, X., Kim, D.D., Bowers, W., Plas, D.J., Crair, M., Federoff, H.J., Gan, L., and Klein, W.H. (2001). Development 129, 467-77.

10. Guo, Z., Clydesdale, G., Cheng, J., Kim, K., Gan, L., McConkey, D.J., Ullrich, S.E., Zhuang, Y., and Su, B. (2002). Mol. Cell. Biol. 22, 5761-5768.

11. Yeh, S., Tsai, M.Y., Xu, Q., Mu, X.M., Lardy, H., Huang, K.E., Lin, H., Yeh, S.D., Altuwaijri, S., Zhou, X., Xing, L., Boyce, B.F., Hung, M.C.,Zhang, S., Gan, L., and Chang, C. (2002). Proc. Natl. Acad. Sci. USA 99, 13498-13503.

12. Wee, R., Castrucci, A.M., Provencio, I., Gan, L., and Van Gelder, R.N. (2002). J Neurosci. 22, 10427-10433.

13. Lu, J., Bassel-Duby, R., Hawkins, A., Chang, P., Valdez, R., Wu, H., Gan, L., Shelton, J.M., Richardson, J.A., and Olson, E.N. (2002). Science 298, 2378-2381