Marthe J. Howard, Ph.D.
|Office: 106 Block Health Science Building|
|Fax: 419-383- 3008|
|B.A. 1973, University of California, Berkeley;
M.A. 1978, California State University, San Francisco
Ph.D. 1984, University of California, Irvine
|The work in my laboratory focuses on growth and transcription factor regulation in the specification and differentiation of autonomic neurons. We use modern molecular biology and cell biology techniques to assess gene regulation in avian and mouse embryos. The overall goal of our studies is: 1) to identify genetic regulatory networks involved in neurogenesis and expression of neurotransmitter molecules, 2) to identify cell extrinsic signaling molecules involved in neurogenesis, and 3) to understand the interplay between cell extrinsic cues and cell intrinsic patterns of gene regulation resulting in differentiation of autonomic neurons. Howard's lab is funded by the National Institute of Health (NIDDK, NINDS).|
|1) Molecular Biology techniques including cloning, RNA & DNA purification and analysis, RT-PCR, EMSA, transient transfection, gene array analysis, ChIP assays, mouse genetic manipulation; 2) Cell Biology techniques including cell and tissue culture, immunocytochemistry, histochemistry, Western blot analysis, biochemical pull-down assays, in ovo electroporation; 3) Image analysis including confocal microscopy.|
|References (partial list):|
Howard, M.J., Stanke, M., Schneider, C., Wu, X., and Rohrer, H. 2000. The transcription factor dHAND is a downstream effector of BMPs in sympathetic neuron specification. Development. 127(18):4073-4081.
Wu, X. and Howard, M.J. 2001. Two Signal Transduction Pathways Involved in the Catecholaminergic Differentiation of Avian Neural Crest-derived Cells In Vitro.Mol. Cell Neurosci. 18:394-406.
Wu, X. and Howard, M.J. 2002. Transcripts Encoding HAND Genes are Differentially Expressed and Regulated by BMP4 and GDNF in Developing Avian Gut. Gene Expression 10:291-305.
Bevan, C., Porter, D., Prasad, A., Howard, M. J., and Henderson, L.P. (2003). Endocrine disrupters alter early development in Xenopus laevis Env. Hlth. Persp. 111:488-496.
Xu, H., Firulli, A.B., Zhang, X. and Howard, M.J., 2003. HAND2 Synergistically Enhances Transcription of Dopamine- b-hydroxylase in the Presence of Phox2a . Dev. Biol. 262:183-193.
Firulli, B.A., Howard, M.J., McDaid, J.R., MciIreavey, I., Cserjesi, P., Virshup, D.M. and Firulli, A, B. 2003. PKA, PKC and the protein phosphatase 2a influence HAND factor function: a mechanism for tissue specific transcriptional regulation . Molec. Cell , 12:1225-1237.
Zhou, X., Nai, Q., Chen, M., Dittus, J.D., Howard, M.J. and Margiotta. J. F. (2004). BDNF and trkB Signaling in Parasympathetic Neurons: Relevance to Regulating Nicotinic Receptors and Synapses. J. Neuroscience 24(18): 4340-4350.
Howard, M.J. (2005). Mechanisms and Perspectives on Differentiation of Autonomic Neurons Dev. Biol. 277:271-286.
Liu, H., Margiotta, J.F and Howard, M.J. 2005. BMP4 Supports Noradrenergic Differentiation by a PKA-dependent Mechanism. Dev. Biol. 286:521-536.
Sarkar, A. and Howard, M.J., Interactions Between Extrinsic and Extrinsic Signaling Molecules in Specification of Noradrenergic Neurons. 2005. Invited Review: International Journal of Autonomic Nervous System. Autonon. Neurosci.Basic and Clinical. 126-127:225-231.
Bevan, C.L., Bryleva, E., Porter, D.M., Hendershot, T., Liu, H., Howard, M.J. and Henderson, L.P. 2006. The endocrine disrupting counpound, Nonylphenol, inhibits neurotrophin-dependent neurite outgrowth via a G protein-dependent mechanism. Endocrinology 147(9):4192-204.
Hendershot, T.J., Liu, H., Sarkar, A.A., Giovannucci, D.R., Clouthier, D.E., ,Abe,M. and Howard, M.J. (2007). Expression of Hand2 is Sufficient for Neurogenesis and Cell Type-specific Gene Expression in the Enteric Nervous System, Dev. Dyn. 236:93-105.
Hendershot,, T.J., Liu, H., Clouthier, D.E., I., Shepherd, Coppola, E., Studer, M., Firulli, A.B., Pittman, D. and Howard, M.J. (2008). Conditional Deletion of Hand2 Reveals Critical Functions in Neurogenesis and Cell Type-specific Gene Expression for Development of Neural Crest-derived Noradrenergic Sympathetic Ganglion Neurons. Dev. Biol. 319:179-191. PMCID: PMC2517160
Schmidt, M., Lin, S., Pape, M., Ernsberger, U., Howard, M. J., and Rohrer, H. (2009).The bHLH transcription factor Hand2 is essential for the maintenance of noradrenergic properties in differentiated sympathetic neurons. Dev. Biol 329; 191-200 PMID: 19254708
Holler, K.L., Hendershot, T.J., Troy, S.E., Vincentz, J.W., Firulli, A.B., and Howard, M.J.(2010). Targeted deletion of Hand2 in cardiac neural crest-derived cells influences cardiac gene expression and outflow tract development. Dev Biol. 341:291-304. PMID: 20144608.
Barron, F., Woods, C., Kuhn, K., Bishop, J., Howard, M.J. and Clouthier, D.E. (2010). Downregulation of Dlx5 and Dlx66 expression by Hand2 is essential for initiation of tongue morphogenesis. Development 138:2249-2259.
Lei, J. and Howard, M.J. (2011). Targeted deletion of Hand2 in enteric neural precursor cells affects its functions in neurogenesis, neurotransmitter specification and gangliogenesis causing functional aganglionosis. Development 138:4789-4800. Reviewed by the Faculty of 1000.
Vincentz, J., VanDusen, N., Rubart, M., Howard, M.J., Firulli, B.A., Firulli, A.B. (2012). A Phox2- and Hand2-dependent cis-regulatory element regulates Hand1 expression in sympathetic neurons. J. Neurosci. 32: 2110-2120.