Hox genes are a highly conserved set of genes that are key regulators of animal development. Numerous organogenesis defects are observed with loss-of-function mutations in this gene family. In order to elucidate the basic mechanisms of Hox function during mammalian organogenesis and development, we employ mouse developmental genetics, molecular biology and biochemical approaches. The laboratory focuses on several model organ systems including the musculoskeletal system, the developing limb, pancreas, gut and urogenital development to dissect how Hox genes function to pattern tissue types during organogenesis and integrate these cell types to form a functional organ. These studies will contribute to our long-term goal of understanding the general downstream mechanisms controlled by Hox genes to direct differentiation and development processes in mammals and to elucidate how this information can be used to improve potential regenerative therapies for affected organ systems.
Our investigations on Hox genes in urogenital development focus on the integration of cell types to form the mammalian kidney. Hox10 and Hox11 genes are expressed in many tissues of the developing kidney and ureteral mesenchyme and loss of function of these genes lead to kidney agenesis, branching defects, and hydronephrosis at the UPJ by laregely unknown mechanisms. This work will provide new information on how Hox genes contribute to this defect, hopefully shedding light on novel insight into therapy for the important human disease.
Another project in the laboratory focuses on understanding the role of Hox genes in pancreatic organogenesis and islet cell development and maintenance. Hox6 genes are only expressed in the mesoderm of the pancreas, yet lead to profound defects in development of the endocrine (endoderm-derived) pancreas. These studies will contribute to our long-term goal of understanding the general downstream mechanisms controlled by Hox genes to direct differentiation and development processes in mammals and to elucidate how this information can be used to improve potential regenerative therapies in the pancreas. Defects in other aspects of gut organogenesis in several Hox mutants are also being pursued in the laboratory.
A further central goal in the laboratory is dissecting the role of Hox genes in limb patterning, musculoskeletal development as well as tissue repair after injury. Using null, conditional loss-of-function and reporter fusion alleles, we have identified and reported many defects in limb development associated with loss of Hox function. Specifically, we are pursuing early patterning defects in these mutants, as well as investigating the mechanism by which these genes direct the integration of muscle, tendon and skeletal tissue, and exploring how these genes are re-employed after injury to regulate the innate musculoskeletal repair and healing process.
1986 A.B., Washington University in St. Louis (Biology)
1995 Ph.D., University of Wisconsin, Madison (Biochemistry, Dr. Hector F. DeLuca)
1996-2002 Postdoctoral fellow, University of Utah (Dr. Mario Capecchi)
Honors and Awards
1992 Wharton Fellowship
1993 Babcock Fellowship
1994 Burris Fellowship
1997 NRSA from NIH Multidisciplinary Basic Cancer Research Training Grant
Xu, B., Wellik, D.M., “Axial Hox9 Activity Establishes the Posterior Compartment in the Developing Forelimb”, PNAS 108(12): 4888-91 (2011). PMID: 21383175
Wellik, D.M., “Hox Genes and Vertebrate Axial Pattern”, In Olivier Pourquie, editor: Current Topics in Developmental Biology, Vol. 88, Burlington: Academic Press, pp. 257-278 (2009). (ISBN: 978-0-12-374529-3). PMID 19651308
Nelson, L.T., Rakshit, S., Sun, H, Wellik, D.M. (2008) Generation and expression of a targeted Hoxa11eGFP allele in mice, Developmental Dynamics 237(11): 3410-3416.
Gong, K-Q., Yallowitz, A.R., Sun, H.S., Dressler, G.R., Wellik, D.M., (2007). "A Hox-Eya-Pax Complex Regulates Kidney Developmental Gene Expression", Molecular & Cellular Biology, in press.
Wellik, D.M., (2007) "Hox Patterning of the Vertebrate Axial Skeleton", Developmental Dynamics, 236:2454-2463.
McIntyre, D.C., Rakshit, S., Yallowitz, A.R., Loken, L., Jeannotte, L., Capecchi, M.R., and Wellik, D.M. (2007), "Hox Patterning of the Vertebrate Rib Cage", Development, 134:2981-2989. (highlighted in this issue and on the cover)
Wellik, D.M., Hawkes, P.J. and Capecchi, M.R. (2002). Hox11 paralogous genes are essential for metanephric kidney induction. Genes & Development 16:1423-1432.
Please contact Dr. Wellik for information regarding current research projects.
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