Cell and Developmental Biology University of Michigan

Research

Molecular regulation of hte epithelial morphogenesis in the developing kidney and mammary gland.

How tissue-specific transcription factors contribute to cell fate specification and differentiated function is not well understood. We analyze the role of transcription factor GATA-3 in specifying various tissues during organogenesis, and the role it plays in various differentiation processes. Our interests address both normal and pathophysiological developmental events, and focus specifically on peripheral and central nervous system development, urogenital patterning and differentiation of the breast epithelium. We use gain- and conditional loss-of-function mutations in mice to examine the consequences of GATA-3 forced expression or lack of expression in specific tissues and organs in order to define the epistatic relationships between GATA-3 and upstream, cooperative parallel and downstream effectors.

Lab Members

• James Douglas Engel
  Professor and Chair
• Tomonori Hosoya
  Research Investigator
• Osamu Tanabe
  Research Assistant Professor
• Shuaiying Cui
  Research Fellow
• Bradley Godfrey
  Research Fellow
• Sakie Hosoya-Ohmura
  Research Fellow
• Chia-Jui Ku
  Research Fellow
• Lihong Shi
  Research Fellow
• Mary Herrmann
  Research Lab Technician
• Carmen Yu
  Research Lab Technician
• Yu-Hsuan Lin
  Graduate Student

Publications

Representative Publications

• Lim, K.C-., Lakshmanan, G., Crawford, S., Gu, Y., Grosveld, F., and J.D. Engel, (2000) Gata3 loss leads to embryonic lethality due to noradrenaline deficiency of the sympathetic nervous system. Nature Genetics 25:209-212
• Takahashi, S., Shimizu, R., Suwabe, N., Kuroha, T., Ohta, J., Nishimura, S., Lim, K.C, Engel, J.D. and M. Yamamoto. Gata factor transgenes under GATA-1 locus control rescue germline GATA-1 mutant deficiencies. Blood 96:910-916
• Lakshmanan, G., Lieuw, K. H., Lim, K.-C, Grosveld, F., Engel, J.D. and A. Karis (1999) Localisation of distant CNS-, endocardial-, and urogenital-specific transcriptional regulatory elements in the GATA-3 locus, Mol. Cell. Biol. 19, 1558-1568.
• Zhou, Y., Lim, K.-C, Onodera, K., Takahashi,S., Minigishi, N., Tsai, F.-Y., Orkin, S.H., Yamamoto, M. and J. D. Engel (1998) Rescue of the embryonic lethal hematopoietic defect reveals a critical role for GATA-2 in urogenital development, EMBO J. 18, 66896700.
• Moriguchi, T., Takako, N., Hamada, M., Maeda, A., Fujioka, Y., Kuroha, T., Huber, R.E., Hasegawa, S.L., Rao, A., Yamamoto, M., Takahashi, S., Lim, K.-C. and J. D. Engel, (2006) Gata3 participates in a complex transcriptional feedback network to regulate sympathoadrenal differentiation, Development 133, 3871-81.
• Hasegawa, S.L., Moriguchi, T., Rao, A., Kuroha, T., J. D. Engel and K.-C. Lim (2006) Dosage-dependent rescue of definitive nephrogenesis by a distant Gata3 enhancer, Developmental Biology.