As an undergraduate, Dr. Johnson studied chemistry at the University of Washington in Seattle. In 1988, she completed her Ph.D. in biochemistry at the University of Washington, where she worked with Dr. Stephan Hauschka on muscle development. She joined the faculty at UT Southwestern in December 1992 following completion of her postdoctoral studies with Dr. David Anderson at California Institute of Technology in Pasadena.
The research in the Johnson lab is focused on vertebrate nervous system development during the transition from proliferating neural stem cells to differentiating neurons and glia. We use the bHLH family of transcription factors to probe the molecular mechanisms controlling the balance of neural progenitor cell maintenance and differentiation, and the generation of neuronal diversity. Alteration in function and expression of the neural bHLH factors result in disturbances of connectivity, imbalances in excitatory and inhibitory neuron formation and loss of control of neural cell number. In particular our focus has been in the dorsal neural tube, critical for somatosensation, where we have defined a shared function for the proneural bHLH factors in neuronal differentiation and distinct functions in neuronal sub-type specification.
One major impact of this research effort has been in identifying and characterizing enhancer sequences for these genes that direct spatially and temporally discrete transcription during neural development. These sequences and subsequent transgenic mouse models have been used widely in the research community for studies in development of spinal cord and brain, inner ear, retina, olfactory epithelium, adult neurogenesis, stem cell biology, and cancer. In addition, we use mouse models and overexpression in chick neural tube to probe the function of the bHLH factors, mechanisms of action of the bHLH factors, and the identity and fates of progenitors expressing each factor. These efforts are revealing fundamental molecular mechanisms and rationales for how a nervous system is generated. Most recently, we are taking advantage of major advances in technology that allow for a deeper understanding of how transcription factors function by identifying direct transcriptional targets genome wide using ChIP-seq and RNA-seq strategies.
Currently there are four main areas of research in my laboratory: 1) regulation and function of Ascl1 in embryonic neural development and cancer, 2) regulation and function of Ptf1a in specification of inhibitory neurons in the dorsal spinal cord and cerebellum, 3) regulation, function, and lineage analysis of Atoh1 and Neurog1 in neuronal sub-type specification and circuit formation in the dorsal spinal cord, and 4) uncovering functions of the direct downstream targets of these neural bHLH factors in neural differentiation and neuronal sub-type specification. The neural bHLH factors sit at critical choice points for generating the correct number of neurons of specific types required for proper neuronal circuit function. Our focus on understanding how transcription factors regulate neuronal differentiation and diversity has direct implications for stem cell biology and cancer.
Chang, J.C., Meredith, D.M., Mayer, P.R., Borromeo, M.D., Lai, H.C. and Johnson, J.E. (2013) Prdm13 mediates the balance of inhibitory and excitatory neurons in somatosensory circuits. Dev Cell (in press).
Lai,H.C., Tiemo, J.K., Roberts, R., Zoghbi, H.Y., and Johnson, J.E. (2011) In vivo neuronal subtype-specific targets of Atoh1 (Math1) in dorsal spinal cord. J Neurosci 31, 10859-10871. Online supporting material (download and open in MS Excel): Part 1, Part 2, Part 3.
Kim, E.J., Ables, J.L., Dickel, L.K., Eisch, A.J., and Johnson, J.E. (2011) Ascl1 (Mash1) defines cells with long term neurogenic potential in subgranular and subventricular zones in adult mouse brain. PLoS One 6, e18472.
Kim, E.J., Hori, K., Wyckoff, A., Dickel, L.K., Koundakjian, E.J., Goodrich, L.V., and Johnson, J.E. (2011) The spatiotemporal fate map of Neurogenin1 (Neurog1) lineages in the central nervous system. J Comp Neurol 519, 1355-1370.
Quinones, H.I., Savage, T.K., Battiste, J., and Johnson, J.E. (2010) Neurogenin 1 expression in the ventral neural tube is mediated by a distinct enhancer and preferentially marks ventral interneuron lineages. Dev Biol 340, 283-292.
Meredith, D.M., Masui, T., Swift, G.H., MacDonald, R.J., and Johnson, J.E. (2009) Multiple Transcriptional Mechanisms Control Ptf1a Levels During Neural Development Including Autoregulation by the PTF1-J Complex. Neurosci 29, 11139-11148.
Henke, R.M.*, Savage, T.K.*, Meredith, D.M., Glasgow, S.M., Hori, K., Dumas, J., MacDonald, R.J., and Johnson, J.E. (2009) Neurog2 is a Direct Downstream Target of the Ptf1a-Rbpj Transcription Complex in Dorsal Spinal Cord. Development 136, 2945-2954.
Henke, R.M., Meredith, D.M., Borromeo, M.D., Savage, T.K., and Johnson, J.E. (2009) Ascl1 and Neurog2 form novel complexes and regulate Delta-like3 (Dll3) expression in the neural tube. Dev. Biol. 328, 529-540.
Kim, E.J., Battiste, J., Nakagawa, Y., and Johnson, J.E. (2008) Ascl1 (Mash1) lineage cells contribute to discrete cell populations in CNS architecture. Mol Cell Neurosci 38, 595-606.
Hori, K., Cholewa-Walclaw, J., Nakada, Y., Glascow, S.M., Masui, T., Henke, R.M., Wildner, H., Martarelli, B., Beres, T.M., Epstein, J.A., Magnuson, M.A., MacDonald, R.J., Birchmeier, C. and Johnson, J.E. (2008) A non-classical bHLH-Rbpj transcription factor complex is required for specification of GABAergic neurons independent of Notch signaling. Genes and Dev. 22, 166-178.
Kim, E.J., Leung, C.T., Reed, R.R., and Johnson, J.E. (2007) In vivo analysis of Ascl1 defined progenators reveals distinct developmental dynamics during adult neurogenesis and gliogenesis. J. Neurosci. 27, 12764-12774.
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. (2007) Ascl1 defines sequentially generated lineage restricted neuronal and oligodendrocyte precursor cells in the spinal cord. Development 134, 285-293.
Glasgow, S., Henke, R.M., Wright, C., MacDonald, R., and Johnson, J.E. (2005) PTF1a determines GABAergic over glutamatergic neuronal cell fate in the spinal cord dorsal horn. Development 132, 5461-5469.
Helms, A.W., Battiste, J., Henke, R.M., Nakada, Y., Simplicio, N., Guillemot, F., and Johnson, J.E. (2005) Sequential roles for Mash1 and Ngn2 in the generation of dorsal spinal cord interneurons. Development 132, 2709-2719.
Nakada, Y., Parab, P., Simmons, A., Omer-Abdalla, A., and Johnson, J.E. (2004) Separable enhancer sequences regulate the expression of the neural bHLH transcription factor Neurogenin1. Dev Biol 271, 479-487.
Liu, Y., Helms, A.W. and Johnson, J.E. (2004) Distinct activities of Msx1 and Msx3 in dorsal neural tube development. Development 131, 1017-1028.
Nakada, Y., Hunsaker, T.L., Henke, R.M. and Johnson, J.E. (2004) Distinct domains within Mash1 and Math1 are required for function in neuronal differentiation versus neuronal cell-type specification. Development 131, 1319-1330.