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Crossin, Kathryn
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Crossin, Kathryn

Faculty Member
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Positions

  • 2013 Associate Professor, Cell and Molecular Biology (CMB) , Scripps Research
  • 1998 - 2013 Associate Professor with tenure, Neurobiology , Scripps Research
  • 1992 - 2013 Faculty Member, Skaggs Graduate School of Chemical and Biological Sciences , Scripps Research
  • 1992 - 1997 Associate Professor, Neurobiology , Scripps Research
  • 1986 - 1992 Assistant Professor (Joint Appointment), The Rockefeller University
  • 1982 - 1986 Postdoctoral Fellow with Dr. Gerald Edelman, The Rockefeller University
Dr. Kathryn Crossin focuses on understanding the signaling capabilities of various cell adhesion molecules on the cell's plasma membrane, particularly the neural cell adhesion molecule, N-CAM, and its ability to signal hippocampal neural precursor cells to become neurons rather that astroglia and to activate the transcription factor NFkB in astrocytes.

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Publications

recent publications

  • academic article

    • Crossin, K. L. Oxygen levels and the regulation of cell adhesion in the nervous system a control point for morphogenesis in development, disease and evolution? Cell Adhesion & Migration  2012 6:49-58  DOI:10.4161/cam.19582  PMID:22647940  PMCID:PMC3364138
    • Ingraham, C. A., Park, G. C., Makarenkova, H. P., Crossin, K. L. Matrix metalloproteinase (MMP)-9 induced by Wnt signaling increases the proliferation and migration of embryonic neural stem cells at low O2 levels Journal of Biological Chemistry  2011 286:17649-17657  DOI:10.1074/jbc.M111.229427  PMID:21460212  PMCID:PMC3093840
    • Chen, S., Owens, G. C., Crossin, K. L., Edelman, D. B. Serotonin stimulates mitochondrial transport in hippocampal neurons Molecular and Cellular Neuroscience  2007 36:472-483  DOI:10.1016/j.mcn.2007.08.004  PMID:17904380
    • Tsatmali, M., Walcott, E. C., Makarenkova, H., Crossin, K. L. Reactive oxygen species modulate the differentiation of neurons in clonal cortical cultures Molecular and Cellular Neuroscience  2006 33:345-357  DOI:10.1016/j.mcn.2006.08.005  PMID:17000118  PMCID:PMC1797198
    • Tsatmali, M., Walcott, E. C., Crossin, K. L. Newborn neurons acquire high levels of reactive oxygen species and increased mitochondrial proteins upon differentiation from progenitors Brain Research  2005 1040:137-150  DOI:10.1016/j.brainres.2005.01.087  PMID:15804435
    • Owens, G. C., Mistry, S., Edelman, G. M., Crossin, K. L. Efficient marking of neural stem cell-derived neurons with a modified murine embryonic stem cell virus, mesv2 Gene Therapy  2002 9:1044-1048  DOI:10.1038/sj.gt.3301780  PMID:12101436
    • Mistry, S. K., Keefer, E. W., Cunningham, B. A., Edelman, G. M., Crossin, K. L. Cultured rat hippocampal neural progenitors generate spontaneously active neural networks Proceedings of the National Academy of Sciences of the United States of America  2002 99:1621-1626  DOI:10.1073/pnas.022646599  PMID:11818538  PMCID:PMC122240
    • Crossin, K. L. Cell adhesion molecules activate signaling networks that influence proliferation, gene expression, and differentiation Annals of the New York Academy of Sciences  2002 961:159-160  DOI:10.1111/j.1749-6632.2002.tb03072.x  PMID:12081888
    • Damsky, C., Heidaran, M., Bottaro, D., Crossin, K., Ducy, P., Ingber, D. Molecular signaling - Breakout session summary Annals of the New York Academy of Sciences  2002 961:164-167  DOI:10.1111/j.1749-6632.2002.tb03075.x  PMID:12081891
    • Schmitt-Ulms, G., Legname, G., Baldwin, M. A., Ball, H. L., Bradon, N., Bosque, P. J., Crossin, K. L., Edelman, G. M., DeArmond, S. J., Cohen, F. E., Prusiner, S. B. Binding of neural cell adhesion molecules (n-cams) to the cellular prion protein Journal of Molecular Biology  2001 314:1209-1225  DOI:10.1006/jmbi.2001.5183  PMID:11743735
    • Little, E. B., Crossin, K. L., Krushel, L. A., Edelman, G. M., Cunningham, B. A. A short segment within the cytoplasmic domain of the neural cell adhesion molecule (n-cam) is essential for n-cam-induced nf-kappa b activity in astrocytes Proceedings of the National Academy of Sciences of the United States of America  2001 98:2238-2243  DOI:10.1073/pnas.041597098  PMID:11226223  PMCID:PMC30122
    • Choi, J., Krushel, L. A., Crossin, K. L. Nf-kappa b activation by n-cam and cytokines in astrocytes is regulated by multiple protein kinases and redox modulation Glia  2001 33:45-56  DOI:10.1002/1098-1136(20010101)33:1<45::aid-glia1005>3.0.co;2-a  PMID:11169791
    • Crossin, K. L., Krushel, L. A. Cellular signaling by neural cell adhesion molecules of the immunoglobulin superfamily Developmental Dynamics  2000 218:260-279  DOI:10.1002/(sici)1097-0177(200006)218:2<260::aid-dvdy3>3.0.co;2-9  PMID:10842356
    • Amoureux, M. C., Cunningham, B. A., Edelman, G. M., Crossin, K. L. N-CAM binding inhibits the proliferation of hippocampal progenitor cells and promotes their differentiation to a neuronal phenotype Journal of Neuroscience  2000 20:3631-3640  PMID:10804205
    • Vanderklish, P. W., Krushel, L. A., Holst, B. H., Gally, J. A., Crossin, K. L., Edelman, G. M. Marking synaptic activity in dendritic spines with a calpain substrate exhibiting fluorescence resonance energy transfer Proceedings of the National Academy of Sciences of the United States of America  2000 97:2253-2258  DOI:10.1073/pnas.040565597  PMID:10688895  PMCID:PMC15787
    • Krushel, L. A., Cunningham, B. A., Edelman, G. M., Crossin, K. L. Nf-kappa b activity is induced by neural cell adhesion molecule binding to neurons and astrocytes Journal of Biological Chemistry  1999 274:2432-2439  DOI:10.1074/jbc.274.4.2432  PMID:9891013
    • Denda, S., Muller, U., Crossin, K. L., Erickson, H. P., Reichardt, L. F. Utilization of a soluble integrin-alkaline phosphatase chimera to characterize integrin alpha 8 beta 1 receptor interactions with tenascin: Murine alpha 8 beta 1 binds to the rgd site in tenascin-c fragments, but not to native tenascin-c Biochemistry  1998 37:5464-5474  DOI:10.1021/bi9727489  PMID:9548928  PMCID:PMC2710129
    • Phillips, G. R., Krushel, L. A., Crossin, K. L. Domains of tenascin involved in glioma migration Journal of Cell Science  1998 111:1095-1104  PMID:9512505
    • Holst, B. D., Vanderklish, P. W., Krushel, L. A., Zhou, W., Langdon, R. B., McWhirter, J. R., Edelman, G. M., Crossin, K. L. Allosteric modulation of ampa-type glutamate receptors increases activity of the promoter for the neural cell adhesion molecule, n-cam Proceedings of the National Academy of Sciences of the United States of America  1998 95:2597-2602  DOI:10.1073/pnas.95.5.2597  PMID:9482932
    • Krushel, L. A., Tai, M. H., Cunningham, B. A., Edelman, G. M., Crossin, K. L. Neural cell adhesion molecule (n-cam) domains and intracellular signaling pathways involved in the inhibition of astrocyte proliferation Proceedings of the National Academy of Sciences of the United States of America  1998 95:2592-2596  DOI:10.1073/pnas.95.5.2592  PMID:9482931
    • Phillips, G. R., Krushel, L. A., Crossin, K. L. Developmental expression of two rat sialyltransferases that modify the neural cell adhesion molecule, n-cam Developmental Brain Research  1997 102:143-155  DOI:10.1016/s0165-3806(97)00069-2  PMID:9352097
    • Crossin, K. L., Tai, M. H., Krushel, L. A., Mauro, V. P. Glucocorticoid receptor pathways are involved in the inhibition of astrocyte proliferation Proceedings of the National Academy of Sciences of the United States of America  1997 94:2687-2692  DOI:10.1073/pnas.94.6.2687  PMID:9122257
    • Crossin, K. L. Tenascin: a multifunctional extracellular matrix protein with a restricted distribution in development and disease Journal of Cellular Biochemistry  1996 61:592-598  DOI:10.1002/(sici)1097-4644(19960616)61:4<592::aid-jcb13>3.3.co;2-d  PMID:8806083
    • Tranque, P., Crossin, K. L., Cirelli, C., Edelman, G. M., Mauro, V. P. Identification and characterization of a ring zinc finger gene (c-rzf) expressed in chicken embryo cells Proceedings of the National Academy of Sciences of the United States of America  1996 93:3105-3109  DOI:10.1073/pnas.93.7.3105  PMID:8610176
    • SchwanzelFukuda, M., Crossin, K. L., Pfaff, D. W., Bouloux, P. M. G., Hardelin, J. P., Petit, C. Migration of luteinizing hormone-releasing hormone (lhrh) neurons in early human embryos Journal of Comparative Neurology  1996 366:547-557  DOI:10.1002/(sici)1096-9861(19960311)366:3<547::aid-cne12>3.0.co;2-m  PMID:8907364
    • Burgoon, M. P., Hazan, R. B., Phillips, G. R., Crossin, K. L., Edelman, G. M., Cunningham, B. A. Functional-analysis of posttranslational cleavage products of the neuron-glia cell-adhesion molecule, ng-cam Journal of Cell Biology  1995 130:733-744  DOI:10.1083/jcb.130.3.733  PMID:7542658
    • Krushel, L. A., Sporns, O., Cunningham, B. A., Crossin, K. L., Edelman, G. M. Neural cell adhesion molecule (N-CAM) inhibits astrocyte proliferation after injury to different regions of the adult rat brain Proceedings of the National Academy of Sciences of the United States of America  1995 92:4323-4327  DOI:10.1073/pnas.92.10.4323  PMID:7753806  PMCID:PMC41936
    • Frick, I. M., Crossin, K. L., Edelman, G. M., Bjorck, L. Protein H: a bacterial surface protein with affinity for both immunoglobulin and fibronectin type III domains EMBO Journal  1995 14:1674-1679  PMID:7737120  PMCID:PMC398260
    • Sporns, O., Edelman, G. M., Crossin, K. L. The neural cell-adhesion molecule (n-cam) inhibits proliferation in primary cultures of rat astrocytes Proceedings of the National Academy of Sciences of the United States of America  1995 92:542-546  DOI:10.1073/pnas.92.2.542  PMID:7831326
    • Prieto, A. L., Crossin, K. L. Cell-cell adhesion molecules in epithelial-mesenchymal transformations Acta Anatomica  1995 154:21-33  PMID:8714287
    • Hazan, R., Krushel, L., Crossin, K. L. Egf receptor-mediated signals are differentially modulated by concanavalin-a Journal of Cellular Physiology  1995 162:74-85  DOI:10.1002/jcp.1041620110  PMID:7814452
    • Phillips, G. R., Edelman, G. M., Crossin, K. L. Separate cell-binding sites within cytotactin tenascin differentially promote neurite outgrowth Cell Adhesion and Communication  1995 3:257-271  DOI:10.3109/15419069509081291  PMID:8846026
    • Krushel, L. A., Prieto, A. L., Edelman, G. M., Crossin, K. L. Differential-effects of cytotactin tenascin fusion proteins on intracellular ph and cell morphology Journal of Cellular Physiology  1994 161:508-518  DOI:10.1002/jcp.1041610314  PMID:7525616
    • Yokosaki, Y., Palmer, E. L., Prieto, A. L., Crossin, K. L., Bourdon, M. A., Pytela, R., Sheppard, D. The integrin alpha 9 beta 1 mediates cell attachment to a non-RGD site in the third fibronectin type III repeat of tenascin Journal of Biological Chemistry  1994 269:26691-26696  PMID:7523411
    • Schwanzelfukuda, M., Reinhard, G. R., Abraham, S., Crossin, K. L., Edelman, G. M., Pfaff, D. W. Antibody to neural cell-adhesion molecule can disrupt the migration of luteinizing-hormone-releasing hormone neurons into the mouse-brain Journal of Comparative Neurology  1994 342:174-185  DOI:10.1002/cne.903420203  PMID:8201030
    • Mauro, V. P., Wood, I. C., Krushel, L., Crossin, K. L., Edelman, G. M. Cell-adhesion alters gene-transcription in chicken-embryo brain-cells and mouse embryonal carcinoma-cells Proceedings of the National Academy of Sciences of the United States of America  1994 91:2868-2872  DOI:10.1073/pnas.91.7.2868  PMID:8146202
    • Crossin, K. L. Functional role of cytotactin/tenascin in morphogenesis: a modest proposal Perspectives on Developmental Neurobiology  1994 2:21-32  PMID:7530140
    • Crossin, K. L. Morphoregulatory molecules and selectional dynamics during development International Review of Neurobiology  1994 37:53-73  PMID:7883487
    • Prieto, A. L., Edelman, G. M., Crossin, K. L. Multiple integrins mediate cell attachment to cytotactin tenascin Proceedings of the National Academy of Sciences of the United States of America  1993 90:10154-10158  DOI:10.1073/pnas.90.21.10154  PMID:7694284
    • Crossin, K. L., Edelman, G. M. Specific binding of cytotactin to sulfated glycolipids Journal of Neuroscience Research  1992 33:631-638  DOI:10.1002/jnr.490330416  PMID:1282934
    • Prieto, A. L., Anderssonfisone, C., Crossin, K. L. Characterization of multiple adhesive and counteradhesive domains in the extracellular-matrix protein cytotactin Journal of Cell Biology  1992 119:663-678  DOI:10.1083/jcb.119.3.663  PMID:1383239
    • Schwanzelfukuda, M., Abraham, S., Crossin, K. L., Edelman, G. M., Pfaff, D. W. Immunocytochemical demonstration of neural cell-adhesion molecule (ncam) along the migration route of luteinizing-hormone-releasing hormone (lhrh) neurons in mice Journal of Comparative Neurology  1992 321:1-8  DOI:10.1002/cne.903210102  PMID:1613133
    • Crossin, K. L. Cytotactin binding - inhibition of stimulated proliferation and intracellular alkalinization in fibroblasts Proceedings of the National Academy of Sciences of the United States of America  1991 88:11403-11407  DOI:10.1073/pnas.88.24.11403  PMID:1722330
    • Tan, S. S., Prieto, A. L., Newgreen, D. F., Crossin, K. L., Edelman, G. M. Cytotactin expression in somites after dorsal neural-tube and neural crest ablation in chicken embryos Proceedings of the National Academy of Sciences of the United States of America  1991 88:6398-6402  DOI:10.1073/pnas.88.15.6398  PMID:1713677
    • Donaldson, D. J., Mahan, J. T., Yang, H., Crossin, K. L. Tenascin localization in skin wounds of the adult newt notophthalmus-viridescens Anatomical Record  1991 230:451-459  DOI:10.1002/ar.1092300403  PMID:1718188
    • Crossin, K. L., Hoffman, S. Expression of adhesion molecules during the formation and differentiation of the avian endocardial cushion tissue Developmental Biology  1991 145:277-286  DOI:10.1016/0012-1606(91)90126-n  PMID:1710192
    • Jhaveri, S., Erzurumlu, R. S., Crossin, K. Barrel construction in rodent neocortex - role of thalamic afferents versus extracellular-matrix molecules Proceedings of the National Academy of Sciences of the United States of America  1991 88:4489-4493  DOI:10.1073/pnas.88.10.4489  PMID:1709743
    • Crossin, K. L. Nitric oxide (NO): a versatile second messenger in brain Trends in Biochemical Sciences  1991 16:81-82  DOI:10.1016/0968-0004(91)90036-u  PMID:1711724
    • Crossin, K. L. Cell adhesion molecules in embryogenesis and disease Annals of the New York Academy of Sciences  1991 615:172-186  DOI:10.1111/j.1749-6632.1991.tb37759.x  PMID:2039143
    • Edelman, G. M., Crossin, K. L. Cell-adhesion molecules - implications for a molecular histology Annual Review of Biochemistry  1991 60:155-190  DOI:10.1146/annurev.bi.60.070191.001103  PMID:1883195
    • Jones, F. S., Crossin, K. L., Cunningham, B. A., Edelman, G. M. Identification and characterization of the promoter for the cytotactin gene Proceedings of the National Academy of Sciences of the United States of America  1990 87:6497-6501  DOI:10.1073/pnas.87.17.6497  PMID:1697683
    • Prieto, A. L., Jones, F. S., Cunningham, B. A., Crossin, K. L., Edelman, G. M. Localization during development of alternatively spliced forms of cytotactin messenger-rna by insitu hybridization Journal of Cell Biology  1990 111:685-698  DOI:10.1083/jcb.111.2.685  PMID:1696267
    • Crossin, K. L., Prieto, A. L., Hoffman, S., Jones, F. S., Friedlander, D. R. Expression of adhesion molecules and the establishment of boundaries during embryonic and neural development Experimental Neurology  1990 109:6-18  DOI:10.1016/s0014-4886(05)80004-4  PMID:2192909
    • Jaffe, S. H., Friedlander, D. R., Matsuzaki, F., Crossin, K. L., Cunningham, B. A., Edelman, G. M. Differential-effects of the cytoplasmic domains of cell-adhesion molecules on cell-aggregation and sorting-out Proceedings of the National Academy of Sciences of the United States of America  1990 87:3589-3593  DOI:10.1073/pnas.87.9.3589  PMID:2185477
    • Hoffman, S., Crossin, K. L., Prediger, E. A., Cunningham, B. A., Edelman, G. M. Expression and function of cell adhesion molecules during the early development of the heart Annals of the New York Academy of Sciences  1990 588:73-86  DOI:10.1111/j.1749-6632.1990.tb13198.x  PMID:1694067
    • Hoffman, S., Crossin, K. L., Jones, F. S., Friedlander, D. R., Edelman, G. M. Cytotactin and cytotactin-binding proteoglycan. An interactive pair of extracellular matrix proteins Annals of the New York Academy of Sciences  1990 580:288-301  DOI:10.1111/j.1749-6632.1990.tb17938.x  PMID:1692457
    • Crossin, K. L., Hoffman, S., Tan, S. S., Edelman, G. M. Cytotactin and its proteoglycan ligand mark structural and functional boundaries in somatosensory cortex of the early postnatal mouse Developmental Biology  1989 136:381-392  DOI:10.1016/0012-1606(89)90264-9  PMID:2479585
    • Prieto, A. L., Crossin, K. L., Cunningham, B. A., Edelman, G. M. Localization of messenger-rna for neural cell-adhesion molecule (n-cam) polypeptides in neural and nonneural tissues by insitu hybridization Proceedings of the National Academy of Sciences of the United States of America  1989 86:9579-9583  DOI:10.1073/pnas.86.23.9579  PMID:2687885
    • Crossin, K. L. Cell and substrate adhesion molecules in embryonic and neural development Clinical Chemistry  1989 35:738-747  PMID:2655999
    • Daniloff, J. K., Crossin, K. L., Pinconraymond, M., Murawsky, M., Rieger, F., Edelman, G. M. Expression of cytotactin in the normal and regenerating neuromuscular system Journal of Cell Biology  1989 108:625-635  DOI:10.1083/jcb.108.2.625  PMID:2465295
    • Raphael, Y., Volk, T., Crossin, K. L., Edelman, G. M., Geiger, B. The modulation of cell-adhesion molecule expression and intercellular junction formation in the developing avian inner-ear Developmental Biology  1988 128:222-235  DOI:10.1016/0012-1606(88)90284-9  PMID:3289987
    • Jones, F. S., Burgoon, M. P., Hoffman, S., Crossin, K. L., Cunningham, B. A., Edelman, G. M. A cdna clone for cytotactin contains sequences similar to epidermal growth factor-like repeats and segments of fibronectin and fibrinogen Proceedings of the National Academy of Sciences of the United States of America  1988 85:2186-2190  DOI:10.1073/pnas.85.7.2186  PMID:2451243
    • Hoffman, S., Crossin, K. L., Edelman, G. M. Molecular-forms, binding functions, and developmental expression patterns of cytotactin and cytotactin-binding proteoglycan, an interactive pair of extracellular-matrix molecules Journal of Cell Biology  1988 106:519-532  DOI:10.1083/jcb.106.2.519  PMID:2448317
    • Tan, S. S., Crossin, K. L., Hoffman, S., Edelman, G. M. Asymmetric expression in somites of cytotactin and its proteoglycan ligand is correlated with neural crest cell distribution Proceedings of the National Academy of Sciences of the United States of America  1987 84:7977-7981  DOI:10.1073/pnas.84.22.7977  PMID:2446315
    • Levi, G., Crossin, K. L., Edelman, G. M. Expression sequences and distribution of 2 primary-cell adhesion molecules during embryonic-development of xenopus-laevis Journal of Cell Biology  1987 105:2359-2372  DOI:10.1083/jcb.105.5.2359  PMID:3680386
    • Chuong, C. M., Crossin, K. L., Edelman, G. M. Sequential expression and differential function of multiple adhesion molecules during the formation of cerebellar cortical layers Journal of Cell Biology  1987 104:331-342  DOI:10.1083/jcb.104.2.331  PMID:3805122
    • Richardson, G. P., Crossin, K. L., Chuong, C. M., Edelman, G. M. Expression of cell-adhesion molecules during embryonic induction .3. Development of the otic placode Developmental Biology  1987 119:217-230  DOI:10.1016/0012-1606(87)90223-5  PMID:3792629
    • Murray, B. A., Owens, G. C., Prediger, E. A., Crossin, K. L., Cunningham, B. A., Edelman, G. M. Cell-surface modulation of the neural cell-adhesion molecule resulting from alternative messenger-rna splicing in a tissue-specific developmental sequence Journal of Cell Biology  1986 103:1431-1439  DOI:10.1083/jcb.103.4.1431  PMID:3771645
    • Rieger, F., Daniloff, J. K., Pinconraymond, M., Crossin, K. L., Grumet, M., Edelman, G. M. Neuronal cell-adhesion molecules and cytotactin are colocalized at the node of ranvier Journal of Cell Biology  1986 103:379-391  DOI:10.1083/jcb.103.2.379  PMID:2426280
    • Carney, D. H., Crossin, K. L., Ball, R., Fuller, G. M., Albrecht, T., Thompson, W. C. Changes in the extent of microtubule assembly can regulate initiation of DNA-synthesis Annals of the New York Academy of Sciences  1986 466:919-932  DOI:10.1111/j.1749-6632.1986.tb38477.x  PMID:2873783
    • Crossin, K. L., Hoffman, S., Grumet, M., Thiery, J. P., Edelman, G. M. Site-restricted expression of cytotactin during development of the chicken-embryo Journal of Cell Biology  1986 102:1917-1930  DOI:10.1083/jcb.102.5.1917  PMID:2422181
    • Grumet, M., Hoffman, S., Crossin, K. L., Edelman, G. M. Cytotactin, an extracellular-matrix protein of neural and non-neural tissues that mediates glia neuron interaction Proceedings of the National Academy of Sciences of the United States of America  1985 82:8075-8079  DOI:10.1073/pnas.82.23.8075  PMID:2415980
    • Crossin, K. L., Chuong, C. M., Edelman, G. M. Expression sequences of cell-adhesion molecules Proceedings of the National Academy of Sciences of the United States of America  1985 82:6942-6946  DOI:10.1073/pnas.82.20.6942  PMID:3863135
    • Crossin, K. L., Edelman, G. M., Cunningham, B. A. Mapping of 3 carbohydrate attachment sites in embryonic and adult forms of the neural cell-adhesion molecule Journal of Cell Biology  1984 99:1848-1855  DOI:10.1083/jcb.99.5.1848  PMID:6386828
    • Crossin, K. L., Carney, D. H. Evidence that microtubule depolymerization early in the cell-cycle is sufficient to initiate DNA-synthesis Cell  1981 23:61-71  DOI:10.1016/0092-8674(81)90270-1  PMID:6111398
    • Crossin, K. L., Carney, D. H. Microtubule stabilization by taxol inhibits initiation of DNA-synthesis by thrombin and by epidermal growth-factor Cell  1981 27:341-350  DOI:10.1016/0092-8674(81)90417-7  PMID:6120766
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Research

research overview

  • Work in my laboratory has focused on factors that influence the proliferation and differentiation of neural stem cells (NSCs) from rodent brain. Our initial work in this arena focused on signaling by cell and substrate adhesion molecules in NSCs and other neural cell types. Our recent work has focused on two arenas: (1) the influence of mitochondrial composition and function on NSC differentiation and (2) the effects of oxygen levels on NSC proliferation, migration, and differentiation.

    Mitochondria and Neural Stem Cells

    Neurons are high energy-requiring cells and thus are critically dependent on aerobic metabolism. Our studies on stem cells from embryonic rat cortex revealed that levels of several mitochondrial proteins increase upon NSC differentiation into neurons. Moreover, the neurons had higher levels of reactive oxygen species (ROS) than did the NSCs from which they were derived. This finding provided a means to prepare highly purified NSCs and neurons using FACS and ROS-sensitive dyes. Given that ROS are a natural byproduct of aerobic (i.e. mitochondrial) respiration, this observation focused our attention on mitochondrial composition and function as a possible driving force for neuronal differentiation.

    Projects extending these observations focus on comparing mitochondrial composition and activity in NSCs and various neuronal types, and the role of mitochondrial fission and fusion in modulating these processes.

    Influence of Oxygen Levels on Neural Stem Cell Proliferation and Differentiation

    Studies from our laboratory and several others have indicated that stem cell proliferation is enhanced and differentiation can be modulated when oxygen levels are lower than the 20% typically used in cell culture. Lower levels of oxygen are in fact physiological because the range of O2 levels measured in tissues ranges from 0.1 to 9%, in brain from 0.1 to 5%, and oxygen levels observed in the neural stem cell niche in vivo are among the lowest. Our recent studies have shown that matrix metalloproteinase MMP9 was increased in NSCs in 1% O2. MMP9 activity was responsible for the increased growth rate of these cells in 1% O2 over 20% O2, as blockade of MMP9 activity with a specific inhibitor completely prevented the increase in proliferation.

    Lowered oxygen also caused alterations in levels of mRNA for several cell and substrate adhesion molecules and appeared to affect cell adhesion and possibly cell migration early in the differentiation process. In 1% O2, the production of actin-rich protrusions in neurons was stimulated. The major effect of lowered oxygen in cortical neural stem cell cultures appears to be a shift in the balance between cell and substrate adhesion.

    Additional studies will clarify the effects of lowered O2 and MMP9 inhibition on cell adhesion and migration during both the growth and differentiation phases of culture. In addition, we are evaluating changes in migration and differentiation under high and low oxygen environments. Levels of adhesion and ECM molecules found to be altered by lower O2 will be assessed in the presence and absence of MMP9 inhibitors to determine which adhesion systems contribute to the observed effects on proliferation and differentiation.

    Given that low O2 levels are consistent with the stem cell niche in vivo, the molecules found to be altered in lower oxygen need to be examined in developing embryos from wild type animals and transgenic animals in which such molecules have been perturbed.

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Teaching

advisees

  • graduate advising relationship

    • Phillips, Greg R, Ph.D.  candidate, 1993 - 1997
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Background

education and training

  • Ph.D. in Biochemistry and Cell Biology, The University of Texas Medical Branch at Galveston 1982
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Contact

full name

  • Kathryn Lynn Crossin

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