Deneen Wellik, Ph.D.
Lab website: http://sitemaker.umich.edu/welliklab/home
Deneen M. Wellik, PhD, is an Associate Professor in Molecular Medicine & Genetics and is jointly appointed in the Department of Cell & Developmental Biology. She is the Assistant Director for the Center for Organogenesis at the University of Michigan and serves as the Director of the Training Grant in Organogenesis. She currently serves as an instructor at Cold Spring Harbor on Mouse Development, Stem Cells and Cancer, and is also a member of the NIH DEV1 study section.
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.
A central goal in the laboratory is dissecting the role of Hox genes in limb patterning, musculoskeletal development as well as musuculoskeletal 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 musculoskeletal repair and healing process.
Other projects in the laboratory focus on understanding the role of Hox genes in endodermal organogenesis. Hox genes are expressed with anteroposterior specific boundaries during endodermal development and these expression patterns are maintained through adulthood. We are exploring the defects along this axis developmentally and the mechanisms of Hox function in these tissues, as well as how these genes are redeployed and function in response to injury and disease.
|1986||A.B., Washington University 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)|
Wellik DM, Hawkes PJ, Capecchi MR. Hox11 paralogous genes are essential for metanephric kidney induction. Genes Dev, 2002 Jun 1; 16(11):1423-1432. (PMID 12050119) PMC 186320.
Wellik DM, Capecchi MR. Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. Science, 2003 Jul 18; 301(5631):363-367. (PMID 12869760).
McIntyre DC, Rakshit S, Yallowitz AR, Loken L, Jeannotte L, Capecchi MR, Wellik DM. Hox patterning of the vertebrate rib cage. Development, 2007 Aug; 134(16):2981-2989. (PMID 17626057).
Gong KQ, Yallowitz AR, Sun H, Dressler GR, Wellik DM. A Hox-Eya-Pax complex regulates early kidney developmental gene expression. Mol Cell Biol, 2007 Nov;27(21):7661-7668. (PMID 17785448) PMC 2169072.
Rousso DL, Gaber ZB, Wellik D, Morrisey EE, Novitch BG. Coordinated actions of the forkhead protein Foxp1 and Hox proteins in the columnar organization of spinal motor neurons. Neuron, 2008 Jul 31; 59(2):226-240. (PMID 18667151) PMC 2547125.
Nelson LT, Rakshit S, Sun H, Wellik DM. Generation and expression of a Hoxa11eGFP targeted allele in mice. Dev Dyn 2008;237(11):3410-3416. PMC2855819.
Wellik DM. Hox genes and vertebrate axial pattern. Curr Top Dev Biol, 2009; 88:257-278. (PMID 19651308).
Yallowitz AR, Gong KQ, Swinehart IT, Nelson LT, Wellik DM. Non-homeodomain regions of Hox proteins mediate activation versus repression of Six2 via a single enhancer site in vivo. Dev Biol, 2009 Nov 1; 335(1):156-165. (PMID 19716816) PMC 2791332.
Mallo M, Wellik DM, Deschamps J. Hox genes and regional patterning of the vertebrate body plan. Dev Biol, 2010 Aug 1; 344(1):7-15. (PMID 20435029) PMC 2909379.
Koyama E, Yasuda T, Minugh-Purvis N, Kinumatsu T, Yallowitz AR, Wellik DM, Pacifici M. Hox11 genes establish synovial joint organization and phylogenetic characteristics in developing mouse zeugopod skeletal elements. Development, 2010 Nov; 137(22):3795-3800. (PMID 20978074) PMC 3049277.
Xu B, Wellik DM. Axial Hox9 activity establishes the posterior field in the developing forelimb. Proc Natl Acad Sci U S A, 2011 Mar 22; 108(12):4888-4891. (PMID 21383175) PMC 3064354.
Wellik DM. Hox genes and kidney development. Pediatr Nephrol, 2011 Sep; 26(9):1559-1565. (PMID 21553325).
Yallowitz AR, Hrycaj SM, Short KM, Smyth IM, Wellik DM. Hox10 genes function in kidney development in the differentiation and integration of the cortical stroma. PLoS One, 2011; 6(8):e23410. (PMID 21858105) PMC 3156768.
Xu B, Hariharan A, Rakshit S, Dressier GR, Wellik DM. The role of Pax2 in mouse prostate development. Prostate, 2012 Feb 1; 72(2):217-224. (PMID 21594883) PMC 3178747.
Di Meglio T, Kratochwil CF, Vilain N, Lache A, Vitobello A, Yonehara K, Hrycaj SM, Raska B, Peters AH, Eichmann A, Wellik D, Ducret S, Rijli FM. Ezh2 orchestrates topographic migration and connectivity of mouse precerebellar neurons. Science, 2013 Jan 11; 339(6116):204-207. (PMID 23307742).
Boucherat 0, Montaron S, Berube-Simard FA, Aubin J, Philippidou P, Wellik DM, Dasen JS, Jeannette L. Partial functional redundancy between Hoxa5 and Hoxb5 paralog genes during lung morphogenesis. Am J Physiol Lung Cell Mol Physiol, 2013 Apr 12. (PMID 23585229).
Swinehart IT, Schlientz AJ, Quintanilla CA, Mortlock DP, Wellik DM. Hox11 genes are required for regional patterning and integration of muscle, tendon and bone. Development, 2013 Nov; 140:4574-82. Epub 2013 Oct 23. (Highlighted In This Issue) (PMID 24154528)
Rockich BE, Hrycaj SM, Shih JP, Nagy MS, Kopp JL, Sander M, Wellik DM, Spence JR. Sox9 plays multiple roles inthe lung epithelium during branching morphogenesis. PNAS 2013 Nov 19; 110(47): E4456-64. PMID 24191021
Xu B, Hyrcaj SM, McIntyre DM, Takeuchi JK, Jeannotte L, Gaber ZB, Novitch BG, Wellik DM. Hox5 interacts with Plzf to restrict Shh expression in the developing forelimb. PNAS 2013 Nov 26; 110(48): 19438-43. Epub 2013 Nov 11. PMID 24218595