School of Life Science, Peking University

Research Interests

Zebrafish (Danio rerio) is an excellent model animal to study vertebrate development by genetic approaches. Using zebrafish as a major animal model, we are interested in: (1) Genetic and developmental mechanisms of vertebrate embryogenesis and organogenesis, especially those related to hematopoiesis, cardiovascular development and pancreas formation. (2) Functional genomics study.

As an entry point, we have recently conducted the following two genome-wide, large scale genetic screening for genes either with tissue-specific expression patterns or with mutations.

Using GFP or RFP as the reporter gene, we have performed a Tol2 transposon-mediated large-scale enhancer trap screen in zebrafish. A total of 1, 670 individual F1 transgenic fish lines were isolated, including 30 pancreas and more than 40 hematopoietic and/or cardiovascular specific transgenic lines. Totally 118 insertion sites have been identified, most of which are flanked by novel genes. This project is in collaboration with Prof. Shuo Lin from UCLA of USA.
We have established a zebrafish mutagenesis platform based on retrovirus mediated insertion, and are aiming at generating a mutant library via random insertion of the pseudo-typed retrovirus. So far we have obtained 244 insertions that reside in genes, most of which are functionally unknown. This project is in collaboration with Prof. Shawn Burgess from NHGRI at NIH of USA.

The pancreas contains endocrine and exocrine compartments that both exert important physiological functions. The development of pancreas is a dynamic process of cell proliferation and differentiation which are controlled at molecular levels involving extrinsic signals from the surrounding tissues and intrinsic transcriptional programs. Pancreas cancer has been one of the most poorly understood diseases. Majority of pancreatic cancers originate from uncontrolled expansion of exocrine pancreas. Understanding the mechanisms of cell proliferation during normal pancreas development is important for the comprehending of pancreatic carcinogenesis. It is known that both endocrine cells and exocrine cells derive from the same population of progenitor cells. However, how the progenitor cells adopt different cell fate in response to extrinsic signals as well as how these cells undergo rapid lineage specific proliferation during embryogenesis is not fully understood. We have obtained 30 pancreas specific transgenic lines from our previous Tol2 enhancer trap screen, which gives us a unique opportunity to address these questions in zebrafish.

Hematopoiesis and blood vessel formation are highly conserved among vertebrates. It has been shown that blood cells and blood vessel cells, which are both derived from ventral mesoderm, share common ancestors called hemangioblasts. These hemangioblasts will give rise to hematopoietic stem cells and angioblasts, which, through complicated cell proliferation and differentiation processes, will further differentiate into various types of mature blood cells and blood vessels, respectively. Zebrafish is an ideal model for the analysis of hematopoiesis and cardiovascular development due to its rapid external embryonic development and transparency. These processes can be visualized in live embryos using transgenic fluorescent protein reporters and embryos can survive for several days without circulating blood cells. We aim to study how cell proliferation and differentiation are involved in hematopoiesis and cardiovascular development based on the hematopoietic and/or cardiovascular specific transgenic and mutant zebrafish obtained from the above-mentioned screens.

Publications

Wen, L., Wei, W., Gu, W., Huang, P., Ren, X., Zhang, Z., Zhu, Z., Lin, S. and Zhang, B., , Visualization of monoaminergic neurons and neurotoxicity of MPTP in live transgenic zebrafish , Dev. Biol. , 2008 , 314(1): 84-92
Wei, W., Wen, L., Huang, P., Zhang, Z., Chen, Y., Xiao, A., Huang, H., Zhu, Z., Zhang, B. and Lin, S , Gfi1.1 regulates hematopoietic lineage differentiation during zebrafish embryogenesis , Cell Res. , 2008 , (in press)
Wang, D., Jao, L.-E., Zheng, N., Dolan, K., Ivey, J., Zonies, S., Wu, X., Wu, K., Yang, H., Meng, Q., Zhu, Z., Zhang, B., Lin, S. and Burgess, S. M , Efficient genome-wide mutagenesis of zebrafish genes by retroviral insertions , Proc. Natl. Acad. Sci. USA , 2007 , 104 (30): 12428-12433
Zhang J. Z., Gao W., Yang H. B., Zhang B., Zhu Z. Y. and Xue Y. F , Screening for genes essential for mouse embryonic stem cell self-renewal using a subtractive RNA interference library , Stem Cells , 2006 , 24(12): 2661-2668
Liu, B., Lee, K. W., Anzo, M., Zhang, B., Zi, X., Tao, Y., Shiry, L., Pollak, M., Lin, S. and Cohen, P , Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of angiogenesis , Oncogene , 2006 , 26(12): 1811-1819
Huang, H., Zhang, B., Hartenstein, P. A., Chen, J. N. and Lin, S , NXT2 is required for embryonic heart development in zebrafish , BMC Dev. Biol., , 2005 , 5(1): 7
Sumanas S., Zhang B., Dai R., Lin S , 15-zinc finger protein Bloody Fingers is required for zebrafish morphogenetic movements during neurulation , Dev Biol., , 2005 , 283(1): 85-96
Egli, D., Selvaraj A., Yepiskoposyan H., Zhang B., Hafen E., Georgiev O. and Schaffner W , Knockout of 'metal-responsive transcription factor' MTF-1 in Drosophila by homologous recombination reveals its central role in heavy metal homeostasis , EMBO J., , 2003 , 22(1): 100-108
Zhang B., Georgiev O., Hagmann M., Günes ?., Faller P., Va?ák M. and Schaffner W , Activation of metal transcription factor-1 (MTF-1) by toxic heavy metals and H2O2 in vitro is modulated by metallothionein , Mol. Cell. Biol., , 2003 , 23(23): 8471-8485
Zhang B., Egli D., Georgiev O. and Schaffner W , The Drosophila homolog of mammalian zinc finger factor MTF-1 activates transcription in response to heavy metals , Mol. Cell. Biol., , 2001 , 21(14): 4505-4514

Bo Zhang, Ph.D.

Research Interests

Publications