Despite advances in our understanding of the ultrastructure of eukaryotic cells, the question of how these cells coordinate to form the tissues of our bodies is still poorly understood. Once formed, we know even less about how these tissues are maintained. My lab is interested in how groups of cells organize themselves into properly sized, polarized tubules and then maintain these structures throughout their life. This is particularly significant as defects in these processes contribute to several human diseases. We have been studying these events primarily using the mouse kidney as a model system. We have found that Wnt signaling is necessary for both the initial formation of the kidney tubules and for their later maintenance. In the former instance, mice that have a null allele for Wnt9b completely fail to form kidneys. In the latter, mice with a partial loss of function allele of Wnt9b develop polycystic kidney disease, one of the most common inherited human diseases that is characterized by defects in epithelial polarity and drastically increased cell proliferation. We are now investigating the cellular and molecular mechanisms behind these defects with the hope that our studies will provide a greater understanding of the formation and maintenance of this essential organ, as well as the pathology of PKD and other related diseases such as cancer. We are currently utilizing mouse genetics (including the engineering of transgenics and genetically ablated mice), organ culture, cell culture/biology, RNA interference, gene microarrays, in situ hybridization and immunohistochemistry to reveal the factors involved in these processes and how these factors influence cell biology within the context of the whole organ. Ultimately, we hope our discoveries will be important not only in a biological sense, but will also prove relevant to tissue engineering and the diagnosis and treatment of disease.
RESEARCH INTERESTS
Developmental Biology
Genetics
Cell polarity
Polycystic Kidney Disease
Cancer
RECENT PUBLICATIONS
Basson MA, Akbulut S, Watson-Johnson J, Simon R, Carroll TJ, Shakya R, Gross I, Martin GR, Lufkin T, McMahon AP, Wilson PD, Costantini FD, Mason IJ, Licht JD, "Sprouty1 Is a Critical Regulator of GDNF/RET-Mediated Kidney Induction" Dev Cell, 8(2):229-239, 2005
Batourina, E., Tsai, S., Lambert, S., Sprenkle, P., Viana, R., Dutta, S., Hensle, T., Wang, F., Niederreither, K., McMahon ,A.P., Carroll, TJ and Mendelsohn, C., "Distal ureter morphogenesis depends on apoptosis induced by signals from the urogenital sinus: A new model of ureter maturation." Nature Genetics, 37(10):1082-89, October 2005
Carroll TJ, Park JP, Hayashi S, Majumdar A, McMahon AP., "Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system." Developmental Cell, Vol. 9:283-292, August 2005
Kobayashi A, Kwan KM, Carroll TJ, McMahon AP, Mendelsohn CL, Behringer RR., "Distinct and sequential tissue-specific activities of the LIM-class homeobox gene Lim1 for tubular morphogenesis during kidney development." Development, 132(12):2809-23, 2005
Batourina, E., Tsai, S., Lambert, S., Sprenkle, P., Viana, R., Dutta, S., Hensle, T., Wang, F., Niederreither, K., McMahon ,A.P., Carroll, TJ and Mendelsohn, C., "Distal ureter morphogenesis depends on apoptosis induced by signals from the urogenital sinus: A new model of ureter maturation." Nature Genetics, 37(10):1082-89, October 2005
Lobov I, Rao S, Carroll T, Vallance J, Ito M, Ondr J, Glass D, Patel M, Shu W, Morrisey E, McMahon A, Karsenty G, Lang R, Kurup S., "Wnt7b mediates macrophage-induced programmed cell death." Nature, 437:417-421, Fall 2005
SIGNIFICANT PUBLICATIONS
Carroll, T. J. and Vize, P, "Synergism between Pax-8 and Lim-1 in embryonic kidney development" Developmental Biology, 214(1):46-59, 1999
Carroll, T.J., Wallingford, J, B. and Vize, P, "Dynamic patterns of gene expression in the developing pronephros of Xenopus laevis" Developmental Genetics, 24 (3/4):199-207, 1999
Wallingford, J., Carroll, T.J., and Vize, P, "Precocious expression of the WT1 gene product blocks differentiation of the pronephros" Developmental Biology, 202:103-112, 1998
Carroll, T.J. and Vize, P., "The Wilms’ tumor suppresser gene is involved in the development of disparate kidney forms: evidence from expression in the Xenopus pronephros" Developmental Dynamics, 206:131-138, 1996
Yu, J., Carroll, T.J., and McMahon, A.P., "Sonic hedgehog regulates proliferation and differentiation of mesenchymal cells in the mouse metanephric kidney." Development, 129:5301-12, 2002
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