The development and survival of neurons depends upon an intricate network of interactions between cells. The differentiation of each of the hundreds of cell types in the nervous system results from the expression of a specific set of genes in response to multiple extracellular and intracellular signals. Transcription factors of the basic helix-loop-helix (bHLH) family are involved in the development of neuronal lineages in both invertebrates and vertebrates. Expression of members of one subclass within the bHLH family is restricted to an early stage of neural development during which the decision to proliferate or differentiate is being made. The essential function of this subclass of bHLH factors has been demonstrated in the loss of specific neuronal lineages in mice mutant for these genes. We are studying the regulation and function of multiple members of this bHLH transcription factor family including Mash1, Math1, Ngn1, Ngn2, and Ptf1a. Because each of these factors is essential for the generation of specific types of neurons, and the timing of their expression is essential for normal neural development, understanding their regulation and function will provide insights into the molecular mechanisms underlying the transition from proliferating precursor cell to distinct neuronal sub-types. We use transgenic mice to identify regulatory sequences within these genes that direct expression at specific times and to specific regions within the developing brain and spinal cord. Furthermore, we use mouse mutants and in ovo electroporation in chick to define the role of the bHLH factors in the generation of specific neuronal cell-types. Future experiments are directed towards 1) identifying factors that interact with the bHLH factors to direct neuronal specification, 2) identifying downstream targets of the bHLH factors, and 3) generating lineage maps from specific progenitor cells in the embryo to mature neurons in the adult brain and spinal cord.
These studies are providing valuable tools for defining and manipulating distinct neuronal progenitor populations in multiple regions of the central nervous system.
RESEARCH INTERESTS
Developmental Neuroscience
RECENT PUBLICATIONS
Helms, A. W., Battiste, J., Henke, R. M., Nakada, Y., Simplicio, N., Guillemot, F., and Johnson, J. E., "Sequential roles for Mash1 and Ngn2 in the generation of dorsal spinal cord interneurons" Development, 132:2709-2719, Summer 2005
28. Glasgow, S. M., Henke, R. M., MacDonald, R. J., Wright, C. V. E., and Johnson, J. E., "PTF1a specifies dorsal horn GABAergic over glutamatergic cell fate" Development, 132:5461-5469, 2005
Battiste, J., Helms, A. W., Kim, E. J., Savage, T. K., Lagace, D. C., Mandyam, C. D., Eisch, A. J., Miyoshi, G., and Johnson, J. E., "Ascl1 defines sequentially generated lineage restricted neuronal and oligodendrocyte precursor cells in the spinal cord" Development, 134:285-293, 2007
EJ Kim, CT Leung, RR Reed and JE Johnson, "In vivo Analysis of Ascl1 Defined Proenitors Reveals Distinct Developmental Dynamics during Adult Neurogenesis and Gliogenesis" Journal of Neuroscience, 27:12764-12774, November 2007
K Hori, J Cholewa-Waclaw, Y Nakada, SM Glasgow, T Masui, RM Henke, H Wildner, B Martarelli, TM Beres, JA Epstein, MA Magnuson, RJ MacDonald, C Birchmeier, and JE Johnson, "A Non-classical bHLH-Rbpj transcription factor complex is required for specification of GABAergic neurons independent of Notch signaling" Genes and Development, 22:166-178, January 2008
SIGNIFICANT PUBLICATIONS
Johnson, J. E., Birren, S. J. and Anderson, D. J., "Two rat homologues of Drosophila achaete-scute specifically expressed in neuronal precursors." Nature, 346:858-861, 1990
Helms, A. W. and Johnson, J. E., "Progenitors of dorsal commissural interneurons are defined by MATH1 expression." Development, 125:919-928, 1998
Helms, A. W., Abney, A., Ben-Arie, N., Zoghbi, H. Y. and Johnson, J. E., "Autoregulation and multiple enhancers control Math1 expression in the developing nervous system." Development, 127:1185-1196, 2000
Gowan, K., Helms, A. W., Hunsaker, T., Collisson, T., Ebert, P. J., Odom, R. and Johnson, J. E., "Cross-Inhibitory Activities of NGN1, NGN2 and MATH1 Allow Specification of Distinct Dorsal Interneurons" Neuron, 31:219-232, 2001
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