Cell Biology, Neurobiology & Anatomy

Research Area: Transcriptional control of gut development and function

It has long been known that the small intestinal epithelium carries out different functions along its anterior to posterior axis. For example, the jejunum is a major site for nutrient uptake, whereas the ileum primarily absorbs bile salts. The mechanism by which these specific regions of the small intestine gain their characteristic functions, however, is unknown. Elucidating this process is critical to our ability to restore function to intestinal tissue damaged by disease or injury. We propose that the repertoire of transcription factors expressed in any given intestinal region drives the establishment and maintenance of that region’s characteristic function through the activation and repression of downstream targets. Although many important transcription factors have been identified in the small intestinal epithelium including the zinc finger transcription factors GATA4 and GATA6 and the homeobox transcription factors PDX1, CDX1, CDX2, and HNF1α, the in vivo contribution these factors make to intestinal regionalization remains largely uncharacterized. The long-term goal of the Battle laboratory is to elucidate the transcriptional regulators and the signal transduction pathways required to generate and sustain the functional specificity of discrete regions of the small intestine. Our current work seeks to define the mechanisms through which GATA4 and GATA6 work independently and in concert to establish and maintain intestinal function. Six GATA family proteins have been described in vertebrates, and GATA4, GATA5, and GATA6 are the members of this family expressed in the gastrointestinal tract. Both Gata4 and Gata6 knockout mice die during embryonic development before the intestine forms because of defects in the extraembryonic endoderm. This tissue shares similar function with the GI tract in that it expresses a similar set of genes and is responsible for maintaining the optimal nutrient balance for the developing embryo. Mice lacking Gata5, however, displayed abnormalities only in the female genitourinary tract. Because Gata5 knockout mice manifested such a limited phenotype and no disruption to the gut, we have focused on uncovering the roles that GATA4 and GATA6 play in intestinal development and function. Our recent work demonstrated that GATA4 is essential for jejunal function and confirmed that GATA4 plays a pivotal role in determining jejunal verus ileal identity (Battle et al., 2008 Gastroenterology).

Battle Lab

Mary Faber, Emily Walker, Cayla Lillge, Michele Battle, Bridget Kohlnhofer & Kevin Wojta

Training / Education
PhD, Michigan State University, East Lansing, Michigan, 2002
BS, University of Scranton, Pennsylvania, 1996

Publications

• Si-Tayeb, K., Noto, F.K., Nagaoka, M., Li, J., Battle, M.A., Duris, C., North, P.E., Dalton, S., and Duncan, S.A. (2010) Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology.
  
  Sun, K, Battle, M.A., Misra, R.P., and Duncan, S.A. (2009) Hepatocyte expression of serum response factor is essential for liver function, hepatocyte proliferation and survival, and postnatal body growth in mice. Hepatology, 49, 1645-1654.
  
   
• Battle, M.A., Bondow, B., Iverson, M., Adams, S.J., Jandacek, R., Tso, P., and Duncan, S.A. (2008) GATA4 is essential for jejunal function in mice. Gastroenterology, 135, 1676-1686.
  
   
• Luebke-Wheeler, J., Zhang, K., Battle, M.A., Si-Tayeb, K., Garrison, W., Sodhi, C., Li, J., Kaufman, R.J., and S.A. Duncan (2008). HNF4a is implicated in ER stress induced acute phase response by regulating expression of CrebH. Hepatology, 48, 1242-1250.
  
   
• Zhao, R., Watt, A.J., Battle, M.A., Li, J., Bondow, BJ, and Duncan, S.A. (2008) Loss of both GATA4 and GATA6 blocks cardiac myocyte differentiation and results in acardia in mice. Developmental Biology 317, 614-619.
  
   
• Battle, M. A., Konopka, G., Parviz, F., Gaggl, A. L., Yang, C., Sladek, F. M., and Duncan, S. A. (2006). Hepatocyte nuclear factor  orchestrates expression of cell adhesion proteins during the epitheliala4 transformation of the developing liver. Proc Natl Acad Sci USA 103, 8419-8424. Faculty of 1000 Biology: evaluations for Battle MA et al Proc Natl Acad Sci U S A 2006 May 30 103 (22):8419-24
   

• Garrison, W. D., Battle, M. A., Yang, C., Kaestner, K. H., Sladek, F. M., and Duncan, S. A. (2006). Hepatocyte nuclear factor 4 is essential for embryonic development of the mouse colon. Gastroenterology 130, 1207-1220.
   

• Rufibach, L. E., Duncan, S. A., Battle, M.A., and Deeb, S. S. (2006). Transcriptional regulation of the human hepatic lipase (LIPC) gene promoter. J Lipid Res 47, 1463-1477.
   

• Watt, A. J., Battle, M. A., Li, J., and Duncan, S. A. (2004). GATA4 is essential for formation of the proepicardium and regulates cardiogenesis. Proc Natl Acad Sci USA 101, 12573-12578.
   

• Battle, M. A., Maher, V. M., and McCormick, J. J. (2003). ST7 is a novel low-density lipoprotein receptor-related protein (LRP) with a cytoplasmic tail that interacts with proteins related to signal transduction pathways. Biochemistry 42, 7270-7282.