The experiments described in this revised proposal are aimed at understanding the role of the GATA family of transcription factors in development. Since each member of the GATA family of transcription factors is critical for normal development, it has been difficult to survey the defects that result from absence of these factors in late embryonic development and adult life. The investigator proposes to address these putative later functions by defining transcriptional control elements for the different GATA family members and generating partially complementing alleles in YAC vectors. In addition, the development of a second and general conditional gene inactivation protocol is proposed. Finally, a significant amount of this proposal is dedicated to defining the transcriptional control elements of complex regulatory genes in mammals in a manner that permits this knowledge to be used to test specific questions about gene function in the animal.
| Moriguchi, Takashi; Yu, Lei; Otsuki, Akihito et al. (2016) Gata3 Hypomorphic Mutant Mice Rescued with a Yeast Artificial Chromosome Transgene Suffer a Glomerular Mesangial Cell Defect. Mol Cell Biol 36:2272-81 |
| Udager, Aaron M; Prakash, Ajay; Saenz, David A et al. (2014) Proper development of the outer longitudinal smooth muscle of the mouse pylorus requires Nkx2-5 and Gata3. Gastroenterology 146:157-165.e10 |
| Lim, Kim-Chew; Hosoya, Tomonori; Brandt, William et al. (2012) Conditional Gata2 inactivation results in HSC loss and lymphatic mispatterning. J Clin Invest 122:3705-17 |
| Ku, Chia-Jui; Hosoya, Tomonori; Maillard, Ivan et al. (2012) GATA-3 regulates hematopoietic stem cell maintenance and cell-cycle entry. Blood 119:2242-51 |
| Hosoya-Ohmura, Sakie; Lin, Yu-Hsuan; Herrmann, Mary et al. (2011) An NK and T cell enhancer lies 280 kilobase pairs 3' to the gata3 structural gene. Mol Cell Biol 31:1894-904 |
| Duncan, Jeremy S; Lim, Kim-Chew; Engel, James D et al. (2011) Limited inner ear morphogenesis and neurosensory development are possible in the absence of GATA3. Int J Dev Biol 55:297-303 |
| Hosoya, Tomonori; Maillard, Ivan; Engel, James D (2010) From the cradle to the grave: activities of GATA-3 throughout T-cell development and differentiation. Immunol Rev 238:110-25 |
| Maeda, Atsuko; Moriguchi, Takashi; Hamada, Michito et al. (2009) Transcription factor GATA-3 is essential for lens development. Dev Dyn 238:2280-91 |
| Hosoya, Tomonori; Kuroha, Takashi; Moriguchi, Takashi et al. (2009) GATA-3 is required for early T lineage progenitor development. J Exp Med 206:2987-3000 |
| Rao, Arvind; Hero 3rd, Alfred O; States, David J et al. (2008) Using directed information to build biologically relevant influence networks. J Bioinform Comput Biol 6:493-519 |
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