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Jhumku D. Kohtz, PhDAssistant Professor
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Regional patterning is known to occur through the action of morphogens. Morphogens are defined as secreted signaling molecules that act in a gradient and at a distance from the source of the morphogen. One of the biggest puzzles in developmental biology is how do morphogens travel across several cell diameters and form gradients.
Our lab has been using a variety of molecular and biochemical tools to show that the N-lipid and C-lipids of the sonic hedgehog (Shh) morphogen are critical to the formation of a multimeric complex that is involved in a novel morphogenic mechanism. Another focus of the lab is the study of a novel ventral forebrain non-coding RNA that is involved in transcriptionally activating homeodomain expression in the ventral forebrain. This is the first demonstration that developmentally regulated non-coding RNAs can cooperate with homeodomain proteins to activate specific enhancers. Thesis projects include the construction of mouse models to test the role of the Shh multimers in morphogenesis in vivo, as well as the role of the novel non-coding RNAs in cis and trans in activating specific homeodomain expression in vivo.
Kohtz, J.D., Lee, H.Y., Gaiano, N., Segal, J.D., Ng, E., Larson, T.A., Baker, D.P., Garber, E.A., Williams, K.P., Fishell, G. (2001) N-terminal fatty-acylation of Sonic Hedgehog enhances the induction of rodent ventral forebrain neurons. Development 128:2351-2363.
Lee, J.D., Kraus, P., Gaiano, N., Nery, S., Kohtz, J.D., Fishell, G., Loomis, C.A., Treisman, J.E. (2001) An acylatable residue of Hedgehog is differentially required in Drosophila and mouse limb development. Developmental Biology 233:122-136.
Hevner, RF, Daza, R.A.M., Englund, C., Kohtz, J.D., and Fink, A. (2004) Radial migration of interneurons in normal and reeler mouse parietal cortex: inward migration from the marginal zone (or superplate) to the cortical plate. Neuroscience 124:605-18.
Kohtz, J.D., and Fishell, G. (2004) Developmental Regulation of EVF-1, a Novel Non-coding RNA Transcribed Upstream of the Mouse Dlx6 Gene. Mechanisms of Development, Gene Expression Patterns, 4/4: 407-412.
Feng, J., White, B., Tyurina, O.V., Guner, B., Larson, T., Lee, H.Y., Karlstrom, R.O., Kohtz., J.D. (2004) Synergistic and antagonistic roles of the Sonic hedgehog N- and C-terminal lipids. Development 131: 4357-4370.
Tyurina, OY, Popova, E., Guner, B., Feng, J., Talbot, W.S., Schier, A.F., Kohtz, J.D., and Rolf O. Karlstrom. (2005) Zebrafish Gli3 functions as both an activator and a repressor of Hh signaling. Developmental Biology, 277: 537-556.
*Feng, J., Bi, C., Clark, B., Mady, R., Shah, P., Kohtz, J.D. (2006) The Evf-2 non-coding RNA is transcribed from the Dlx 5/6 ultraconserved region and functions as a Dlx-2 homeodomain transcriptional coactivator. Genes and Development, 20: 1470-1484.
* News and Views Highlight, Lall, S. (2006) Noncoding RNAs and Homeodomains Get Together. Nature Structural and Molecular Biology 13, 574.
Stumm R, Kolodziej A, Schulz S, Kohtz JD, Hollt V (2007) Patterns of SDF-1 alpha and SDF-1 gamma mRNAs, migration pathways, and phenotypes of CXCR4-expressing neurons in the developing rat telencephalon Journal of Comparative Neurology 502: 382-399.
Bi, C., Schwab, D., Clark, B., Millen, K. Bai, B., Kohtz, J.D. Shh regulates the formation of the telencephalic choroid roof and plexus (under revision).
10. Bond, A., vanGompel, M. J., Kohtz, J.D. Balanced gene expression by the ultraconserved non-coding RNA Evf2 is required for GABAergic interneuron development (manuscript in preparation)
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View Publications by Jhumku Kohtz listed in the National Library of Medicine (PubMed). |
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