Mengqing Xiang Professor UMDNJ Department of Pediatrics CABM - Room 240 679 Hoes Lane Piscataway. NJ 08854 (732) 235-4491 FAX - 4466 xiang@cabm.rutgers.edu Visit Dr. Xiang's Lab

Molecular bases of sensorineural development. transcriptional regulation of retinal and inner ear development

Our research interests center on understanding the molecular events that lead to the determination. differentiation and survival of the highly specialized sensory cells and neurons. The mammalian sensory system carries external and internal sensory information to the central nervous system. where it is processed to coordinate motor responses. The establishment of these sensory circuits in the adult depends critically on the generation of distinct neuronal types and sensory receptors at proper times and positions during embryogenesis as well as on their maintenance throughout life. Despite the importance of sensory cells/neurons. however. the molecular basis of their formation and survival is still poorly understood. My laboratory employs a variety of molecular genetic and bioinformatics approaches to identify and study transcription and other regulatory factors that are required for programming development of the retina. inner ear. somatosensory ganglia. spinal cord. and brain. A major focus of our work is to develop animal models to study roles of transcription factor genes during normal sensorineural development. as well as to elucidate how mutations in these genes cause sensorineural disorders such as blindness and deafness.

My laboratory utilizes two general approaches to understand the biological roles that a transcription factor gene plays during vertebrate neurogenesis. One is a loss-of-function approach involving targeted gene disruption in mouse embryonic stem (ES) cells to produce mice deficient for the gene of interest. The other is a gain-of-function approach involving plasmid/retrovirus-mediated overexpression of the gene of interest in the chick and mouse embryonic tissues. These complementary approaches have allowed us to identify a number of transcription factors including Foxn4. Barhl and Brn3 as crucial regulatory factors that are required for fate commitment. differentiation and/or survival of various sensory cells and neurons.

Selected Publications

Qiu F, Jiang H, Xiang M. (2008) A comprehensive negative regulatory program controlled by Brn3b to ensure ganglion cell specification from multipotential retinal precursors. J Neurosci. 28(13):3392-403.

Collin RW, Chellappa R, Pauw RJ, Vriend G, Oostrik J, van Drunen W, Huygen PL, Admiraal R, Hoefsloot LH, Cremers FP, Xiang M, Cremers CW, Kremer H. (2008) Missense mutations in POU4F3 cause autosomal dominant hearing impairment DFNA15 and affect subcellular localization and DNA binding. Hum Mutat. 29(4):545-54.

Chellappa R, Li S, Pauley S, Jahan I, Jin K, Xiang M. (2008) Barhl1 regulatory sequences required for cell-specific gene expression and autoregulation in the inner ear and central nervous system. Mol Cell Biol. 28(6):1905-14.

Del Barrio MG, Taveira-Marques R, Muroyama Y, Yuk DI, Li S, Wines-Samuelson M, Shen J, Smith HK, Xiang M, Rowitch D, Richardson WD. (2007) A regulatory network involving Foxn4, Mash1 and delta-like 4/Notch1 generates V2a and V2b spinal interneurons from a common progenitor pool. Development. 134(19):3427-36.

Fujitani Y, Fujitani S, Luo H, Qiu F, Burlison J, Long Q, Kawaguchi Y, Edlund H, MacDonald RJ, Furukawa T, Fujikado T, Magnuson MA, Xiang M, Wright CV. (2006) Ptf1a determines horizontal and amacrine cell fates during mouse retinal development. Development. 133(22):4439-50.

Li S, Xiang M. (2006) Barhl1 is required for maintenance of a large population of neurons in the zonal layer of the superior colliculus. Dev Dyn. 235(8):2260-5.

Fritzsch B, Pauley S, Matei V, Katz DM, Xiang M, Tessarollo L. (2005) Mutant mice reveal the molecular and cellular basis for specific sensory connections to inner ear epithelia and primary nuclei of the brain. Hear Res. 206(1-2):52-63. Review.

Li. S.. Misra. K.. Matise. M. and Xiang. M. (2005) Foxn4 acts synergistically with Mash1 to specify subtype identity of V2 interneurons in the spinal cord. Proc. Natl. Acad. Sci. USA 102:10688-10693.

Li. S.. Mo. Z.. Yang. X.. Price. S. M.. Shen. M. M. and Xiang. M. (2004) Foxn4 controls the genesis of amacrine and horizontal cells by retinal progenitors. Neuron 43:795-807.

Mo. Z.. Li. S.. Yang. X.. and Xiang. M. (2004) Role of the Barhl2 homeobox gene in the specification of glycinergic amacrine cells. Development 131:1607-1618.

Li. S.. Qiu. F.. Xu. A.. Price. S. M.. and Xiang. M. (2004) Barhl1 regulates migration and survival of cerebellar granule cells by controlling expression of the neurotrophin-3 gene. J. Neurosci. 24:3104-3114.

Weiss S.. Gottfried. I.. Mayrose. I.. Khare. S. L.. Xiang. M.. Dawson. S. J.. and Avraham. K. B. (2003) The DFNA15 deafness mutation affects POU4F3 protein stability. localization and transcriptional activity. Mol. Cell. Biol. 23:7957-7964.

Li S. Price SM. Cahill H. Ryugo DK. Shen MM. and Xiang M. (2002) Hearing loss caused by progressive degeneration of cochlear hair cells in mice deficient for the Barhl1homeobox gene. Development 129:3523-32.

Huang. E. J.. Liu. W.. Fritzsch. B.. Bianchi. L. M.. Reichardt. L. F.. and Xiang. M. (2001) Brn3a is a transcriptional regulator of soma size. target field innervation. and axon pathfinding of inner ear sensory neurons. Development 128:2421-2432.

Liu W. Mo Z. Xiang M. (2001) The Ath5 proneural genes function upstream of Brn3 POU domain transcription factor genes to promote retinal ganglion cell development. Proc Natl Acad Sci USA 98:1649-54.

Liu W. Khare SL. Liang X. Peters MA. Liu X. Cepko CL. Xiang M. (2000) All Brn3 genes can promote retinal ganglion cell differentiation in the chick. Development 127:3237-47.