Ph.D. ,1992,
University of Maine at Orono

Yu Lan, Ph.D

Research Assistant Professor, Biomedical Genetics, Center for Oral Biology

Contact Information:
Dentistry at the University of Rochester
601 Elmwood Ave, Box 611
Rochester, New York 14642
KMRB G-9641
Phone: (585) 273-1425, Fax: (585) 506-0190

Email:
Yu_Lan@urmc.rochester.edu

Research:
Molecular Mechanisms of Mammalian Palate Development

OVERVIEW

The mammalian secondary palate arises from the medial sides of the maxillary processes flanking the embryonic oral cavity as two bilateral outgrowths that grow initially vertically down the sides of the developing tongue. At a precise developmental stage the bilateral palatal shelves elevate to a horizontal position above the dorsum of the tongue and fuse with each other at the midline to form the intact secondary palate that separates the nasal cavity from the oral cavity. Any disturbance of the growth, elevation or fusion of the palatal shelves could result in cleft palate, one of the most common birth defects in humans. Neither the molecular processes governing normal palatogenesis nor the causes of cleft palate are well understood. We have carried out gene expression screens to identify potential regulators of palate development and have identified two transcription factors, Osr2 and Tbx22 as key regulators of palate development in mice. The human OSR2 gene is associated with orofacial clefting and mutations in the human TBX22 gene cause X-linked cleft palate. We have generated a targeted mutation in the Osr2 gene and found that Osr2 mutant mice have impaired palatal shelf growth and exhibit cleft palate at birth. Current research focuses on investigating how these transcription factors regulate palatal growth and patterning.

PUBLICATIONS
Miskiewicz, P., Morrissey, D., Lan, Y., Raj, L., Kessler, S., Fujioka, M., Goto, T. and Weir, M. 1996. Both the paired domain and homeodomain are required for in vivo function of Drosophila Paired. Development, 122:2709-2718.

Lan, Y., Jiang, R., Shawber, C., Weinmaster, G. and Gridley, T. 1997. The Jagged2 gene maps to chromosome 12 and is a candidate for the lgl and sm mutations. Mammalian Genome, 8:875-876.

Jiang, R., Lan, Y., Chapman, H. D., Shawber, C., Norton, C. R., Serreze, D. V., Weinmaster, G., and Gridley, T. 1998. Defects in limb, craniofacial and thymic development in Jagged2 mutant mice. Genes & Development, 12:1046-1057.

Lan, Y., Fujioka, M., Polsgrove, R., Miskiewicz, P., Morrissey, D., Goto, T. and Weir, M. 1998. Plasticity of Drosophila Paired function. Developmental Genetics 23:45-55.

Jiang, R., Lan, Y., Norton, C. R., Sundberg, J. P., and Gridley, T. 1998. The Slug gene is not essential for mesoderm or neural crest development in mice. Developmental Biology 198:277-285.

Bell, S., Lan, Y., Jiang, R., and Gridley, T. 1998. Exclusion of Jagged2 as a candidate for the legless gene. Mammalian Genome 9:778-779.

Lanford, P. J., Lan, Y., Jiang, R., Lindsell, C., Weinmaster, G., Gridley, T., and Kelley, M. W. 1999. Notch signaling pathway mediates hair cell development in mammalian cochlea. Nature Genetics 21:289-292.

McCright, B., X. Gao, J. Lozier, Y. Lan, L. Shen, M. Maguire, D. Herzlinger, G. Weinmaster, R. Jiang, and T. Gridley. 2001. Defects in development of the kidney, heart and eye vasculature in mice homozygous for a hypomorphic Notch2 mutation. Development 128:491-502.

Lan, Y., P.D. Kingsley, E.S. Cho, and R. Jiang. 2001. Osr2, a new mouse gene related to Drosophila odd-skipped exhibits dynamic expression patterns during craniofacial, limb, and kidney development. Mech. of Dev. 107:175-179.

Carver, E.A., R. Jiang, Y. Lan, K.F. Oram, and T. Gridley. 2001. The mouse Snail gene encodes a key regulator of the epithelial-mesenchymal transition. Mol. Cell. Biol. 21: 8184-8188.

Bush, J. O., Y. Lan, K. M. Maltby, and R. Jiang. 2002. Isolation and developmental expression analysis of Tbx22, the mouse homolog of the human X-linked cleft palate gene. Developmental Dynamics

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