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Research Assistant Professor,
Cell & Developmental
Biology
109 Zina Pitcher Place
2041 Biomedical Sciences Research Bldg (BSRB)
(734) 615-7242
Email: kclim@umich.edu
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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.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.
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