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Faculty, Biological Sciences, Lehigh University

M. Kathryn Iovine, Ph.D.

M. Kathryn Iovine, Ph.D.
Professor

Research Interest:
Biochemistry
Cell & Molecular Biology

Iacocca Hall
111 Research Drive, D222
Bethlehem, PA 18015

610-758-6981

email Dr. Iovine
 
Research

Research interests:

regeneration, skeletal morphogenesis, cell-cell communication, extracellular matrix, hyaluronic acid, semaphorins, developmental biology, genetics


My lab is interested how the bones of the skeleton achieve the correct size. To examine this problem we study regeneration of the zebrafish fin skeleton. Fins grow by the addition of new 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 bone growth in the fin.

Identification of the mutations causing phenotypes affecting segment length will reveal genetic and molecular pathways underlying segment growth. For example, we showed that mutations in the gap junction gene connexin43 cause the short fin phenotypes of reduced fin length, reduced segment length, and reduced cell proliferation. Our research suggests that Cx43 activity coordinates skeletal growth (i.e. cell proliferation) and patterning (i.e.  joint formation).

M. Kathryn Iovine, Ph.D.

The goal of my lab is to reveal how defects in Cx43-based gap junctional intercellular communication mediate skeletal morphogenesis. Using a microarray, we identified and validated several genes whose expression appears to depend on the level of Cx43 activity. We are finding that Cx43 function seems to regulate the expression of genes that function in, or modify, the extracellular environment. Thus, we identified the secreted growth factor, Sema3d, as mediating independent intercellular signaling pathways that control cell proliferation and joint formation (Ton and Iovine, 2012). We also find that the hyaluronan-based extracellular matrix contributes to these pathways (Govindan and Iovine, 2014). Most recently, we showed that the collagen-based actinotrichia are necessary for normal levels of cell proliferation and for normal placement of joints (Bhadra and Iovine, 2015). Because of the location of actinotrichia between the compartment of dividing cells and the compartment of cells that differentiate into bone and joint forming cells, we suggest that the integrity of actinotrichia signals to both compartments to coordinate growth and patterning. We are in the process of validating additional genes, and we continue to build a Cx43-dependent network in order to provide new insights into the pathways that can be regulated by gap junctional communication.

Publications

PDFBhattacharya, S., Gargiulo, D., Iovine, M.K. Simplet-dependent regulation of beta-catenin signaling influences skeletal patterning downstream of Cx43. Development. doi:10.1231/dev.166975.

PDF Dardis, G., Tryon, R., Ton, Q., Johnson, S.L., Iovine, M.K. Cx43 suppresses evx1 expression to regulate joint initiation in the regenerating fin. Developmental Dynamics. doi: 10.1002/dvdy.24531. 2017.

PDF Banerji, R., Eble, D.M., Iovine, M.K., Skibbens, R.V. Esco2 Regulates cx43 Expression During Skeletal Regeneration in the Zebrafish Fin. 2016. Developmental Dynamics 245:7-21. doi: 10.1002/DVDY.24354

PDF Barton, R., Khakbaz, P., Bera, I. Klauda, J.B., Iovine, M.K., Berger, B.W. 2016 Interplay of Specific Trans- and Juxtamembrane Interfaces in Plexin A3 Dimerization and Signal Transduction. Biochemistry 55: 4928-4938. doi: 10.1021/acs.biochem.6b00517

PDF Misu, A., Yamanaka, H. Aramaki, T., Kondo, S., Skerrett, I.M., Iovine, M.K., Watanabe, M. 2016. Two Different Functions of Connexin43 Confer Two Different Bone Phenotypes in Zebrafish. J. of Biological Chemistry. 291: 24, 12601-12611. doi: 10.1074/jbc.M116.720110

PDFGovindan, J., Tun, KM., Iovine, M.K. Cx43-Dependent Skeletal Phenotypes Are Mediated by Interactions between the Hapln1a-ECM and Sema3d during Fin Regeneration. 2016. PLoS ONE 11(2):
e0148202. doi:10.1371/journal.pone.0148202

M. Kathryn Iovine, Ph.D., Lehigh UniversityPDFBhadra, J, Banerji, R., Singh, J., Sallada, N., Eble, D.M., and Iovine, M.K. The zebrafish fibroblast cell line AB9 as a tool to complement gene regulation studies. Musculoskeletal Research. doi:10.14800/mr.992. 2015.

PDFBhadra, J. and Iovine, M.K. Hsp47 mediates Cx43-dependent skeletal growth and patterning in the regenerating fin. Mechanisms of Development. doi: 10.1016/j.mod.2015.06.004. 2015.

PDFGovindan, J. and Iovine, M.K. Dynamic remodeling of the extra cellular matrix during zebrafish fin regeneration. Gene expression patterns. doi: 10.1016/j.gep.2015.06.001. 2015.

PDFBarton, R., Driscoll, A., Flores, S., Mudbhari, D., Collins, T., Iovine, MK, Berger, B.W., Cysteines in the neuropilin-2 MAM domain modulate receptor homooligomerization and signal transduction. Biopolymers. doi: 10.1002/bip.22619. 2015.

PDFBarton, R., Palacio, D., Iovine, M. K., Berger, B.W., A Cytosolic Juxtamembrane Interface Regulates Plexin A3 Oligomerization and Signal Transduction. PLoS One. doi: 10.1371/journal.pone.0116368. 2015.

PDFGovindan, J. and Iovine, M.K. Hapln1a is required for Connexin43-dependent growth and patterning in the regenerating fin skeleton. PLoS One. doi:10.1371/journal.pone.0088574. 2014.

PDFTon, Q.T. and Iovine, M.K. Identification of an evx1-dependent joint-formation pathway during fin regeneration. PLoS One. doi: 10.1371/journal.pone.0081240. 2013.

PDFTon, Q.T. and Iovine, M.K. Semaphorin3d mediates Cx43-dependent phenotypes during fin regeneration. Dev. Biol. 366: 195-203. 2012.

PDFGerhardt, 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.

PDFBrown, 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.

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

PDFHoptak-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.

PDFIovine, 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.

PDFHoptak-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.

PDFJain, 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.

PDF 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.

PDF 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.

PDF 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.

PDF 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.

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

M. Kathryn Iovine, Ph.D.
 

Reviews

PDF Banerji, R., Skibbens, R.V., Iovine, M.K. How many roads lead to cohesinopathies? Developmental Dynamics. doi: 10.1002/dvdy.24510. 2017. Invited review.

PDF Holtzman, N.G., Iovine, M.K., Liang, J.O., Morris, J. Learning to Fish with Genetics: A Primer on the Vertebrate Model Danio rerio. 2016. Genetics. doi:10.1534/genetics.116.190843/-/DC1.

PDFTon, Q.T. and Iovine, M.K. Determining how defects in Connexin43 cause skeletal disease. genesis. doi:10.1002/dvg.22349. 2012. Invited review.

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

 

Collaborative Publications

PDFGumm, 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.

PDFItkowitz 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

PDF 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.

Lab Members - Present and Past

Current Lab Members

Rebecca Bowman

Rebecca Bowman
Lab Technician

 

 

 

Raj Banerji

Rajeswari Banerji
Graduate Student

 

 

 

Past Lab Members

M. Kathryn Iovine, Ph.D.

2015 - from left to right: Harneel Riar, Rebecca Bowman, Joyita Bhadra, Jayalakshmi Govindan, M. Kathryn Iovine, Ph.D., Rajeswari Banerji

  • Joyita Bhadra, Ph.D. - post-doctoral fellow at the Indian Institute of Science, Bangalore
  • Jayalakshmi Govindan, Ph.D. - research associate at Princeton University
  • Angela Hoptak, Ph.D. - instructor at Kutztown University
  • Quynh Ton, Ph.D. - post-doctoral fellow at the University of Children's Hospital, Cincinnati

 

 

Images
  • Knockdown of Esco2 causes short fin ray segments (left) compared with control fin ray segments. Knockdown of Esco2 causes short fin ray segments (left) compared with control fin ray segments.
  • Zebrafish Cx43-EGFP expression in HeLa cells (tubulin is shown in red). Zebrafish Cx43-EGFP expression in HeLa cells (tubulin is shown in red).
  • Expression of evx1 in joint-forming cells (purple) in a regenerating fin ray. Expression of evx1 in joint-forming cells (purple) in a regenerating fin ray.
  • Change in Cx40.8 localization from the plasma membrane during ontogenetic fin growth (A) to the Golgi apparatus (B) during regeneration. Change in Cx40.8 localization from the plasma membrane during ontogenetic fin growth (A) to the Golgi apparatus (B) during regeneration.
  • Interzone-like organization of joint-forming cells in a presumptive joint during fin regeneration. Interzone-like organization of joint-forming cells in a presumptive joint during fin regeneration.
  • Expression of Col2 (green) and Hsp47 (red) in the regenerating fin. A longitudinal section (top) and a transverse section (bottom) are shown. Nuclei are stained in blue. Expression of Col2 (green) and Hsp47 (red) in the regenerating fin. A longitudinal section (top) and a transverse section (bottom) are shown. Nuclei are stained in blue.
  • Adult lof/+ fish. Adult lof/+ fish.
  • ZNS5 staining detects both bone-forming cells and joint-forming cells (green). Inset shows a longitudinal cross-section stained for both ZNS5 (green) and Cx43 (red). The staining overlaps in the joint-forming cells (arrowheads). ZNS5 staining detects both bone-forming cells and joint-forming cells (green). Inset shows a longitudinal cross-section stained for both ZNS5 (green) and Cx43 (red). The staining overlaps in the joint-forming cells (arrowheads).
  • Caudal fin stained with calcein to detect calcified bone matrix. Caudal fin stained with calcein to detect calcified bone matrix.

Current Funding:

Understanding how Cx43 regulates joint formation in the regenerating zebrafish fin (R15HD080507)
Developing a vertebrate model system for Roberts Syndrome (Lehigh Faculty Research Grant)
Biological Sciences
111 Research Drive
Bethlehem, PA 18015		 Phone: 610-758-3680
Fax: 610-758-4004
Email: inbios@lehigh.edu

©2015