zile@msu.edu
http://www.msu.edu/~zile/index.htm
Phone: (517) 355-8474 ext. 127
Home Department: Food
Science and Human Nutrition
Professor of Food Science and Human Nutrition; Ph.D., University of Wisconsin - Madison;
M.S., University of Wisconsin - Madison; B.S., University of Maryland
Vitamin A is essential for normal embryonic development in all vertebrates, and exerts its effects at the gene level via nuclear receptors for the vitamin A-active form, retinoic acid. Our laboratory studies the function of retinoids in embryogenesis. We have developed a vitamin A-deficient (retinoid ligand knockout) avian embryo model to examine early developmental events and genes regulated by retinoids. Our focus is on cardiovascular development, i.e. morphogenesis of the primitive heart, specification of heart asymmetry and formation of the initial vascular network. Several retinoid-regulated genes linked to those events have been identified in our lab: homeobox genes HoxB-1 and Msx-1; cardiogenic transcription factor GATA-4, and the asymmetry genes nodal, snail and Pitx-2. Our model provides an opportunity to address basic issues in developmental biology and to elucidate the critical role of vitamin A in embryogenesis, so as to apply this knowledge to prevention of congenital heart defects.
Current projects include: 1) heart asymmetry specification; 2) regulation of cardiac morphogenesis; 3) analysis of the roles of retinoid receptors in regulating heart development; and 4) function of retinoids in vasculogenesis.
Selected Publications
Available online: Description of Publication: minireview 2004 <Article%20ZileExptBiolMed2004.pdf>
Zhou, H-R., Abouzied, M. and Zile, M.H . Production of a hybridoma cell line secreting retinoic acid specific monoclonal antibody. J. Immunol. Meth. 138, 211-223, 1991
Zile, M.H. Vitamin A homeostasis endangered by environmental pollutants. Proc. Soc. Exptl. Biol. Med. 201,141-153, 1992.
Dersch, H. and Zile, M.H. Induction of normal cardiovascular development in the vitamin A-deficient quail embryo by natural retinoids. Devel. Biol. 160,424-433, 1993.
Twal, W., Roze, L. and Zile, M.H . Anti-retinoic acid monoclonal antibody localizes all-trans-retinoic acid in target cells and blocks normal development in early quail embryo. Dev. Biol. 168,225-234, 1995.
Chen, Y., Kostetskii, I., Zile, M.H. , and Solursh, M. Comparative study of Msx-1 expression in early normal and vitamin A-deficient avian embryos. J. Exptl. Zool. 272,299-310, 1995.
Xu, X.C., Zile, M.H., Lippman, S.M., Lee, J.S., Lee, J.J., Hong, W.K. and Lotan, R . Anti-retinoic acid monoclonal antibody binding to premalignant oral lesions is lower than to normal tissue, is increased after treatment with 13-cis-retinoic acid in vivo, and is related to RAR receptor beta expression. Cancer Res. 55, 5507-5511, 1995.
Dong, D. and Zile, M.H. Endogenous retinoids in the early avian embryo. Biochem. Biophys. Res. Communic. 217, 1026-1031, 1995.
Kostetskii, I., Linask, K., and Zile, M.H . Vitamin A deficiency and the expression of retinoic acid receptors during early cardiogenesis in quail embryo. Roux's Arch. Dev. Biol. 205, 260-271, 1996.
Tsuda, T., Philp, N., Zile, M.H. and Linask, K.K . Left-right asymmetric localization of flectin in the extracellular matrix during heart looping. Dev. Biol. 173, 39-50, 1996.
Chen, Y-P., Dong, D., Kostetskii, I. and Zile, M.H . Hensen's node from vitamin A-deficient quail embryo induces chick limb bud duplication and retains its normal asymmetric expression of Sonic hedgehog (Shh). Dev. Biol. 173, 256-264, 1996.
Maden, M., Gale, E., Kostetskii, I. and Zile, M . Vitamin A-deficient quail embryos have half a hindbrain and other neural defects. Current Biology 6, 417-426, 1996.
Maden, M., Graham, A., Gale, E., Rollinson, C. and Zile, M . Positional apoptosis during vertebrate CNS development in the absence of endogenous retinoids. Development 124, 2799-2805, 1997.
Twal, W.O. and Zile, M.H . Retinoic acid reverses ethanol-induced cardiovascular abnormalities in quail embryos. Alcoholism: Clin. Exptl. Res. 21, 1137-1143, 1997.
Zile, M.H., Summer, C., Aulerich, R., Bursian, S.J., Tillit, D.E., Giesy, J. and Kubiak, T.J . Retinoids in eggs and embryos of birds fed fish from the Great Lakes. Env. Toxicol. Pharmacol. 3, 277-288, 1997.
Zile, M.H . Vitamin A in embryonic development: An overview In: Symposium: Functional Metabolism of Vitamin A in Embryonic Development. J. Nutr. 128, 455S-458S, 1998.
Maden, M., Gale, E. and Zile, M.H . The role of vitamin A in the development of the central nervous system. In: Symposium: Functional Metabolism of Vitamin A in Embryonic Development. J. Nutr. 128, 471S-475S, 1998.
Kostetskii, I., Yuan, S.Y., Kostetskaia, E., Linask, K., Blanchet, S., Seleiro, E., Brickell, P., Michaille, J. and Zile, M . Initial retinoid requirement for early avian development coincides with retinoid receptor coexpression in the precardiac fields and induction of normal cardiovascular development. Dev. Dyn. 213, 188-198, 1998.
Kostetskii, I., Jiang, Y., Kostetskaia, E., Yuan, S., Evans, T. and Zile, M . Retinoid signaling required for normal heart development regulates GATA-4 in a pathway distinct from cardiomyocyte differentiation. Dev. Biol. 206, 206-218, 1999.
Stratford, T., Logan, C., Zile, M. and Maden, M . Abnormal anteroposterior and dorsoventral patterning of the limb bud in the absence of retinoids. Mech. Dev. 81, 115-125, 1999.
Zile, M.H . Avian embryo as a model for retinoid function in early development. In: Handbook of Experimental Pharmacology. Vol. 139. Retinoids (H. Nau and W. Blaner, Eds.) Ch. 15, 443- 464. Springer Verlag., Heidelberg, 1999.
Gale, E., Zile, M. and Maden, M . Hindbrain respecification in the retinoid deficient quail. Mech. Dev. 88, 43-54, 1999.
DeLuca, F., Uyeda, J.A., Mericq, V., Mancilla, E.E., Yanovski, J.A., Zile, M.H. and Baron, J . Retinoic acid is a potent regulator of growth plate chondrogenesis. Endocrinology 141, 346-353, 2000.
Griffith, M. and Zile, M.H . Retinoic acid, midkine and defects of secondary neurulation. Teratology 62,123-133, 2000.
Ghatpande, S., Ghatpande, A., Zile, M. and Evans, T . Anterior endoderm is sufficient to rescue foregut apoptosis and heart tube morphogenesis in a embryo lacking retinoic acid. Dev. Biol. 219, 59-70, 2000.
Maden, M., Graham, A., Zile, M. and Gale, E . Abnormalities of somite development in the absence of retinoic acid. Int. J. Dev. Biol. 44, 151-159, 2000.
Zile, M.H., Kostetskii, I., Yuan, S., Kostetskaia, E., St. Amand, T., Chen, Y-P. and Jiang, W . Retinoid signaling is required to complete vertebrate cardiac left-right asymmetry pathway. Dev. Biol. 223, 323-338, 2000.
Zile, M.H . Function of vitamin A in vertebrate embryonic development. J.Nutr.131,705-708, 2001.
Schlange, T., Schnipkoweit, I., Andre, B., Ebert, A., Zile, M.H., Arnold, H-H.,and Brand, T . Chick CFC controls Lefty1 expression in the embryonic midline and Nodal expression in the lateral plate. Dev. Biol. 234, 376-389, 2001.
Ghatpande, S., Ghatpande, A., Sher, J., Zile, M.H. and Evans, T . Retinoid signaling regulates primitive (yolk sac) hematopoiesis. Blood 99,2379-2386, 2002.
Halilagic, A., Zile, M.H. and Studer, M . A novel role for retinoids in patterning the avian forebrain during presomite stages . Development 130,2039-2050, 2003.
Cui,J., Michaille, J-J., Jiang, W. and Zile, M.H . Retinoid receptors and vitamin A deficiency: differential patterns of transcription during early avian development and the rapid induction of RARs by retinoic acid. Dev.Biol.260 , 496-511, 2003.
Romeih, M., Cui,J., Michaille,J-J., Jiang, W., and Zile, M.H . Function of RARγ and RARα at the initiation of retinoid signaling is essential for avian embryo survival and for distinct events in cardiac morphogenesis Dev.Dyn.228,697-708, 2003.
Zile, M.H . Vitamin A requirement for cardiovascular morphogenesis specification in the vertebrate embryo: Insights from the avian embryo. Exptl. Biol. & Medicine.229,598-606,2004.
LaRue, A.C., Zile, M.H., Argraves, W.S.and Drake, C.J. Critical role for retinol in the generation/differentiation of angioblasts required for embryonic blood vessel formation. Dev. Dyn. 230,666-674,2004