Vanderbilt University School of Medicine

Miller, David M. III, Ph.D.
Professor of Cell and Developmental Biology
Professor of Biological Science

Lab Url: http://www.mc.vanderbilt.edu/vumcdept/cellbio/millerlab

Phone Number: (615) 343-3447

Email Address:david.miller@vanderbilt.edu

Miller, David's picture

Office Address   Mailing Address

3120 MRB III

3150A MRB III Cell and Developmental Biology 8240


Research Keywords
Molecular Neurobiology | Neural Specificity | C. elegans,C. elegans,Developmental biology,Gene regulation,Genetics,Genome,Genomics,Mutation,Neuroscience,Receptor,Signal transduction,Transcription factor

Research Specialty
development of the nervous system

Research Description
The function of the nervous system depends on precisely defined patterns of connectivity. Despite the importance of this process, the biological rules governing neural specificity are poorly understood. What are the molecular cues that result in the creation of synapses between specific sets of neurons? The complexity of the vertebrate nervous system coupled with the dearth of biochemical information about synaptic choice have hindered efforts to answer this question in mammals. Our strategy to circumvent these problems is, first, to address this question in a simple, well-defined nervous system and, second, to employ a genetic approach which does not require prior assumptions about the molecular mechanism of neural specificity.

In the nematode, Caenorhabditis elegans, the nervous system is composed of exactly 302 neurons. Every contact between these cells has been catalogued to construct a complete wiring diagram. With this detailed information in hand, it is possible to correlate mutations that produce abnormal or "uncoordinated" movement with specific changes in the structure of the nervous system. A mutation in one of these genes, the transcription factor unc-4, alters the pattern of synaptic input to one class of motor neurons in the ventral nerve cord and results in a strong movement defect. We hypothesize that unc-4 defines a specific motor neuron trait that is recognized by potential presynaptic partners and that these traits are encoded by downstream genes that unc-4 regulates. A major goal in the Miller lab is to identify these unc-4 target genes. Recently, we implemented a pioneering cell-specific profiling strategy to reveal one of these downstream genes, the transcription factor, CEH-12/HB9 (Von Stetina et al., 2007). Expression of CEH-12/HB9 in the vertebrate spinal cord suggests that the role of this pathway may be conserved in more complex motor circuits. Our long term aim is to work out the molecular and cellular mechanism of neural specificity in this simple model system and then to extend our findings to complex vertebrate nervous systems which could not otherwise be dissected by this genetic approach. Other projects in the Miller lab include mechanisms of neurodegeneration, synaptic plasticity, sensory neuron morphogenesis and a genome-wide effort to define the C. elegans transcriptome (modENCODE.org).

Publications
Smith, CJ, O''Brien, T, Chatzigeorgiou, M, Spencer, WC, Feingold-Link, E, Husson, SJ, Hori, S, Mitani, S, Gottschalk, A, Schafer, WR, Miller, DM. Sensory Neuron Fates Are Distinguished by a Transcriptional Switch that Regulates Dendrite Branch Stabilization. Neuron, 79(2), 266-80, 2013.

Wang, Y, Matthewman, C, Han, L, Miller, T, Miller, DM, Bianchi, L. Neurotoxic unc-8 mutants encode constitutively active DEG/ENaC channels that are blocked by divalent cations. J Gen Physiol, 142(2), 157-69, 2013.

Schneider, J, Skelton, RL, Von Stetina, SE, Middelkoop, TC, van Oudenaarden, A, Korswagen, HC, Miller, DM. UNC-4 antagonizes Wnt signaling to regulate synaptic choice in the C. elegans motor circuit. Development, 139(12), 2234-45, 2012.

Smith, CJ, Watson, JD, VanHoven, MK, Col??n-Ramos, DA, Miller, DM. Netrin (UNC-6) mediates dendritic self-avoidance. Nat Neurosci, 15(5), 731-7, 2012.

Albeg, A, Smith, CJ, Chatzigeorgiou, M, Feitelson, DG, Hall, DH, Schafer, WR, Miller, DM, Treinin, M. C. elegans multi-dendritic sensory neurons: morphology and function. Mol Cell Neurosci, 46(1), 308-17, 2011. PMCID:3006369

Hallem, EA, Spencer, WC, McWhirter, RD, Zeller, G, Henz, SR, R??tsch, G, Miller, DM, Horvitz, HR, Sternberg, PW, Ringstad, N. Receptor-type guanylate cyclase is required for carbon dioxide sensation by Caenorhabditis elegans. Proc Natl Acad Sci U S A, 108(1), 254-9, 2011. PMCID:3017194

Lu, ZJ, Yip, KY, Wang, G, Shou, C, Hillier, LW, Khurana, E, Agarwal, A, Auerbach, R, Rozowsky, J, Cheng, C, Kato, M, Miller, DM, Slack, F, Snyder, M, Waterston, RH, Reinke, V, Gerstein, MB. Prediction and characterization of noncoding RNAs in C. elegans by integrating conservation, secondary structure, and high-throughput sequencing and array data. Genome Res, 21(2), 276-85, 2011. PMCID:3032931

Petersen, SC, Watson, JD, Richmond, JE, Sarov, M, Walthall, WW, Miller, DM. A transcriptional program promotes remodeling of GABAergic synapses in Caenorhabditis elegans. J Neurosci, 31(43), 15362-75, 2011. PMCID:3229156

Spencer, WC, Zeller, G, Watson, JD, Henz, SR, Watkins, KL, McWhirter, RD, Petersen, S, Sreedharan, VT, Widmer, C, Jo, J, Reinke, V, Petrella, L, Strome, S, Von Stetina, SE, Katz, M, Shaham, S, R??tsch, G, Miller, DM. A spatial and temporal map of C. elegans gene expression. Genome Res, 21(2), 325-41, 2011. PMCID:3032935

Chatzigeorgiou, M, Yoo, S, Watson, JD, Lee, WH, Spencer, WC, Kindt, KS, Hwang, SW, Miller, DM, Treinin, M, Driscoll, M, Schafer, WR. Specific roles for DEG/ENaC and TRP channels in touch and thermosensation in C. elegans nociceptors. Nat Neurosci, 13(7), 861-8, 2010.

Earls, LR, Hacker, ML, Watson, JD, Miller, DM. Coenzyme Q protects Caenorhabditis elegans GABA neurons from calcium-dependent degeneration. Proc Natl Acad Sci U S A, 107(32), 14460-5, 2010.

Hammock, EA, Eagleson, KL, Barlow, S, Earls, LR, Miller, DM, Levitt, P. Homologs of genes expressed in Caenorhabditis elegans GABAergic neurons are also found in the developing mouse forebrain. Neural Dev, 5, 32, 2010. PMCID:3006369

Smith, CJ, Watson, JD, Spencer, WC, O'Brien, T, Cha, B, Albeg, A, Treinin, M, Miller, DM. Time-lapse imaging and cell-specific expression profiling reveal dynamic branching and molecular determinants of a multi-dendritic nociceptor in C. elegans. Dev Biol, 345, 18-33, 2010.

Thorne, CA, Hanson, AJ, Schneider, J, Tahinci, E, Orton, D, Cselenyi, CS, Jernigan, KK, Meyers, KC, Hang, BI, Waterson, AG, Kim, K, Melancon, B, Ghidu, VP, Sulikowski, GA, LaFleur, B, Salic, A, Lee, LA, Miller, DM, Lee, E. Small-molecule inhibition of Wnt signaling through activation of casein kinase 1I?. Nat Chem Biol, 6(11), 829-36, 2010. PMCID:3006369

Helmcke, KJ, Syversen, T, Miller, DM, Aschner, M. Characterization of the effects of methylmercury on Caenorhabditis elegans. Toxicol Appl Pharmacol, 240(2), 265-72, 2009.

Meissner, B, Warner, A, Wong, K, Dube, N, Lorch, A, McKay, SJ, Khattra, J, Rogalski, T, Somasiri, A, Chaudhry, I, Fox, RM, Miller, DM, Baillie, DL, Holt, RA, Jones, SJ, Marra, MA, Moerman, DG. An integrated strategy to study muscle development and myofilament structure in Caenorhabditis elegans. PLoS Genet, 5(6), e1000537, 2009. PMCID:2694363

Watson, JD, Wang, S, Von Stetina, SE, Spencer, WC, Levy, S, Dexheimer, PJ, Kurn, N, Heath, JD, Miller, DM. Complementary RNA amplification methods enhance microarray identification of transcripts expressed in the C. elegans nervous system. BMC Genomics, 9, 84, 2008. PMCID:2263045

Fox, RM, Watson, JD, Von Stetina, SE, McDermott, J, Brodigan, TM, Fukushige, T, Krause, M, Miller, DM. The embryonic muscle transcriptome of Caenorhabditis elegans. Genome Biol, 8(9), R188, 2007. PMCID:2375026

Miller, DM. Neuroscience. Synapses here and not everywhere. Science, 317(5840), 907-8, 2007.

Von Stetina, SE, Fox, RM, Watkins, KL, Starich, TA, Shaw, JE, Miller, DM. UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans. Genes Dev, 21(3), 332-46, 2007. PMCID:1785118

Von Stetina, SE, Watson, JD, Fox, RM, Olszewski, KL, Spencer, WC, Roy, PJ, Miller, DM. Cell-specific microarray profiling experiments reveal a comprehensive picture of gene expression in the C. elegans nervous system. Genome Biol, 8(7), R135, 2007. PMCID:2323220

Varadan, V, Miller, DM, Anastassiou, D. Computational inference of the molecular logic for synaptic connectivity in C. elegans. Bioinformatics, 22(14), e497-506, 2006.

Fox, RM, Von Stetina, SE, Barlow, SJ, Shaffer, C, Olszewski, KL, Moore, JH, Dupuy, D, Vidal, M, Miller, DM. A gene expression fingerprint of C. elegans embryonic motor neurons. BMC Genomics, 6(1), 42, 2005. PMCID:1079822

Touroutine, DV, Fox, RM, Von Stetina, SE, Burdina, AO, Miller, DM, Richmond, JE. ACR-16 encodes an essential subunit of the levamisole-resistant nicotinic receptor at the C. elegans neuromuscular junction. J Biol Chem, , , 2005.

Von Stetina, SE, Treinin, M, Miller, DM. The motor circuit. Int Rev Neurobiol, 69, 125-67, 2005.

Sedensky, M M, Siefker, J M, Koh, J Y, Miller, D M, Morgan, P G. A stomatin and a degenerin interact in lipid rafts of the nervous system of Caenorhabditis elegans. Am J Physiol Cell Physiol, 287(2), C468-74, 2004.

Christensen, M, Estevez, A, Yin, X, Fox, R, Morrison, R, McDonnell, M, Gleason, C, Miller, DM, Strange, K. A primary culture system for functional analysis of C. elegans neurons and muscle cells. Neuron, 33(4), 503-14, 2002.

Esmaeili, B, Ross, JM, Neades, C, Miller, DM, Ahringer, J. The C. elegans even-skipped homologue, vab-7, specifies DB motoneurone identity and axon trajectory. Development, 129(4), 853-62, 2002.

Nass, Richard, Hall, David H, Miller, David M, Blakely, Randy D. Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans. Proc Natl Acad Sci U S A, 99(5), 3264-9, 2002. PMCID:122507

Bianchi, L, Miller, D M, George, A L. Expression of a CIC chloride channel in Caenorhabditis elegans gamma-aminobutyric acid-ergic neurons. Neurosci Lett, 299(3), 177-80, 2001.

Lickteig, K M, Duerr, J S, Frisby, D L, Hall, D H, Rand, J B, Miller, D M. Regulation of neurotransmitter vesicles by the homeodomain protein UNC-4 and its transcriptional corepressor UNC-37/groucho in Caenorhabditis elegans cholinergic motor neurons. J Neurosci, 21(6), 2001-14, 2001.

Nass, R, Miller, D, Blakely, R. C. elegans: a novel pharmacogenetic model to study Parkinson's disease. , 7(3), 185-191, 2001.

Miller, D M, Desai, N S, Hardin, D C, Piston, D W, Patterson, G H, Fleenor, J, Xu, S, Fire, A. Two-color GFP expression system for C. elegans. Biotechniques, 26(5), 914-8, 920-1, 1999.

Winnier, A R, Meir, J Y, Ross, J M, Tavernarakis, N, Driscoll, M, Ishihara, T, Katsura, I, Miller, D M. UNC-4/UNC-37-dependent repression of motor neuron-specific genes controls synaptic choice in Caenorhabditis elegans. Genes Dev, 13(21), 2774-86, 1999. PMCID:317130

Jayanthi, LD, Apparsundaram, S, Malone, MD, Ward, E, Miller, DM, Eppler, M, Blakely, RD. The Caenorhabditis elegans gene T23G5.5 encodes an antidepressant- and cocaine-sensitive dopamine transporter. Mol Pharmacol, 54(4), 601-9, 1998.

Pflugrad, A, Meir, J Y, Barnes, T M, Miller, D M. The Groucho-like transcription factor UNC-37 functions with the neural specificity gene unc-4 to govern motor neuron identity in C. elegans. Development, 124(9), 1699-709, 1997.

Miller, D M, Niemeyer, C J. Expression of the unc-4 homeoprotein in Caenorhabditis elegans motor neurons specifies presynaptic input. Development, 121(9), 2877-86, 1995.

Miller, D M, Shakes, D C. Immunofluorescence microscopy. Methods Cell Biol, 48, 365-94, 1995.

Miller, DM, Niemeyer, CJ, Chitkara, P. Dominant unc-37 mutations suppress the movement defect of a homeodomain mutation in unc-4, a neural specificity gene in Caenorhabditis elegans. Genetics, 135(3), 741-53, 1993. PMCID:1205717

Miller, DM, Shen, MM, Shamu, CE, B??rglin, TR, Ruvkun, G, Dubois, ML, Ghee, M, Wilson, L. C. elegans unc-4 gene encodes a homeodomain protein that determines the pattern of synaptic input to specific motor neurons. Nature, 355(6363), 841-5, 1992.

Maruyama, IN, Miller, DM, Brenner, S. Myosin heavy chain gene amplification as a suppressor mutation in Caenorhabditis elegans. Mol Gen Genet, 219(1-2), 113-8, 1989.

Miller, DM, Stockdale, FE, Karn, J. Immunological identification of the genes encoding the four myosin heavy chain isoforms of Caenorhabditis elegans. Proc Natl Acad Sci U S A, 83(8), 2305-9, 1986. PMCID:323285

Epstein, HF, Miller, DM, Ortiz, I, Berliner, GC. Myosin and paramyosin are organized about a newly identified core structure. J Cell Biol, 100(3), 904-15, 1985. PMCID:2113503

Watts, FZ, Miller, DM, Orr, E. Identification of myosin heavy chain in Saccharomyces cerevisiae. Nature, 316(6023), 83-5, 1985.

Miller, DM, Ortiz, I, Berliner, GC, Epstein, HF. Differential localization of two myosins within nematode thick filaments. Cell, 34(2), 477-90, 1983.


Postdoctoral Position Available
Yes

Postdoctoral Position Details
A postdoctoral position is available to work on mechanisms of dendrite morphogenesis

Updated Date
08/01/2013