M. Kathryn Iovine, Ph.D.
Associate Professor

Dept. of Biological Sciences
111 Research Drive, B217
Office - D222
Lab - C144
Bethlehem, PA 18015

phone: 610-758-6981
fax: 610-758-4004
lab: 610-758-5433

mki3@lehigh.edu

Research Summary

My lab is interested in the regulation of growth, or how organs/limbs achieve the correct size. To examine this problem we utilize the zebrafish fin, which is easy to measure, grows throughout the lifetime of the fish, and has the capacity for regeneration. Fins grow by the addition of bony fin ray segments to the distal ends of the fin rays, and fin length is regulated by mechanisms controlling both the number and length of those segments.  Therefore, the segment represents the unit of growth in the fin. Fin length mutants can affect either the length of bony segments (i.e. short fin) or the number of segments (i.e. long fin). Identification of the mutations causing these phenotypes will reveal genetic and molecular pathways underlying segment growth and addition. For example, the short fin mutation has been found in the gap junction protein Connexin43, suggesting that direct cell-cell communication is required for growth of fin ray segments. Interestingly, mutations in human CX43 also result in defective skeletal morphogenesis (Paznekas et al., 2003. Am. J. Human Gen. 72: 408), revealing that the function of Cx43 is conserved in vertebrate animals. Research projects in my lab are intended to reveal how defects in intercellular communication leads to defects in bone growth.  We are examining mechanisms regulating of the function of Cx43 gap junctions (i.e. via identification of interacting connexins/proteins and relevant Cx43 domains) and how cellular processes are affected in short fin mutant fins (i.e. proliferation and differentiation).

Publications

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Gerhardt, S.V., Jefferis, R., and Iovine, M.K., Cx40.8, a Cx43-like protein, forms gap junction channels inefficiently and may require Cx43 for its association at the plasma membrane. FEBS Letters. 583: 3419-3424. 2009.

Brown, A.M., Fisher, S., and Iovine, M.K., Osteoblast maturation occurs in overlapping proximal-distal compartments during fin regeneration in zebrafish. Dev. Dyn. 238: 2922-2928. 2009.

Sims, K, Eble, D.M., and Iovine, M.K., Connexin43 regulates joint location in zebrafish fins. /Dev Biol./ *327:* 410-418. 2009.

Hoptak-Solga, A.D., Nielsen, S., Jain, I., Thummel, R., Hyde D., and Iovine, M.K. Connexin43 is required in the population of dividing cells during fin regeneration. /Dev. Biol./ *317:* 541-548. 2008.

Iovine, M.K., Gumpert, A. Falk, M., Mendelson, T.C. Cx23, a connexin with only four extracellular-loop cysteines, forms functional gap junction channels and hemichannels. FEBS Letters. 582: 165-170. 2008.

Hoptak-Solga, A.D., Klein, K.A., DeRosa, A.M. White, T.W., and Iovine, M.K. Zebrafish short fin mutations in connexin43 lead to aberrant gap junctional intercellular communication. FEBS Letters. 581: 3297-3302. 2007.

Jain, I., Stroka, C., Yan, J., Huang, W.M., and Iovine, M.K. Bone growth in zebrafish fins occurs via multiple pulses of cell proliferation. Dev. Dyn. 236: 2668-2674. 2007.

Goldsmith, M.I., Iovine, M.K., O'Reilly-Pol, T., Johnson, S.L. A developmental transition in growth control during zebrafish caudal fin development. Dev. Biol. 296: 450-457.2006.

Eastman, S.D., Chen, T.H., Falk, M.M., Mendelson, T.C., and Iovine, M.K. Phylogenetic analysis of three complete gap junction gene families reveals lineage-specific duplications and highly supported gene classes. Genomics. 87: 265-274. 2006.

Iovine, M.K., Higgins, E.P., Hindes, A., Coblitz, B., and Johnson, S.L. Mutations in connexin43 (GJA1) perturb bone growth in zebrafish fins. Dev. Biol. 278: 208-219. 2005.

Iovine and Johnson, 2002. A Genetic, Deletion, Physical, and Human Homology Map of the long fin Region on Zebrafish Linkage Group 2. Genomics.  79:  756-759.

Iovine and Johnson, 2000.  Genetic Anaylsis of Isometric Growth Control Mechanisms in the Zebrafish Caudal Fin. Genetics.  155: 1321-1329.

Reviews

Iovine, M.K. Conserved mechanisms regulate outgrowth in zebrafish fins. Nature Chem. Biol. 3: 613-618. (2007).

Collaborative Publications

Gumm, J.M, Snekser, J, J.L., and Iovine, M.K., Association preferences of fin-mutant female zebrafish, Danio rerio. /Behavioral Processes/. *80:* 35-38. 2009.

Itkowitz M. and Iovine, M.K. Single gene mutations causing exaggerated fins also cause non-genetic changes in the display behavior of male zebrafish. Behavior. 144: 787-795. 2007

Mendelson, T.C., Imhoff, V.E., and Iovine, M.K. Analysis of early embryogenesis in Rainbow and Banded Darters (Percidae: Etheostoma) reveals asymmetric postmating barrier. Environ. Biol. Fish. 76: 351-360. 2006.

Dr. Iovine's research is supported by
NICHD (R03HD070172)
NSF (IOS-1145582)
and by PA-CURE state funds.

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