Jane Johnson, Ph.D., obtained her B.S. in Chemistry in 1983 and her Ph.D. in Biochemistry in 1988 at the University of Washington. Her Ph.D. research was with Dr. Stephan Hauschka on muscle development. Postdoctoral research with Dr. David Anderson at the California Institute of Technology led to the discovery of ASCL1 (previously MASH1), an essential transcription factor in neural development. Dr. Johnson joined the faculty at UT Southwestern Medical Center in December 1992 where she is currently a Professor in the Department of Neuroscience and holds the Shirley and William S. McIntyre Distinguished Chair in Neuroscience.
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. Our focus on understanding how transcription factors regulate neuronal differentiation and diversity has direct implications for stem cell biology and cancer.
In the dorsal spinal cord, critical for processing somatosensory information, we have defined a shared function for the neural bHLH transcription 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. We also have made significant contributions to understanding the function of these factors in regulating the transition of progenitor cells to differentiating neurons, and oligodendrocytes. These studies use mouse models and over expression in chick neural tube to probe gene function, mechanisms of action of the bHLH factors, and the identity and fates of progenitors expressing each factor. These efforts have revealed fundamental molecular mechanisms and rationales for how a nervous system is generated. More recently, we are taking advantage of major advances in technology that allow for a deeper understanding of how transcription factors function in vivo by identifying direct transcriptional targets genome wide using ChIP-seq and RNA-seq strategies.
Currently there are three main areas of research in my laboratory. 1) regulation and function of ASCL1 in embryonic neural development and cancer such as neuroendocrine lung cancer, 2) epigenetic and transcriptional control balancing the generation of inhibitory and excitatory neurons in the dorsal spinal cord, and 3) uncovering functions of the direct downstream targets of neural bHLH factors in neural differentiation, neuronal sub-type specification, and cancer. The neural bHLH transcription 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. A case in point is ASCL1; importance in reprogramming non-neuronal cells to neurons, and requirement for tumor growth in small cell lung carcinoma.
Kelenis DP, Hart E, Edwards-Fligner M, Johnson JE, and Vue TY. (2018) ASCL1 regulates proliferation of NG2-glia in the embryonic and adult spinal cord. Glia 1–19. DOI:10.1002/glia.23344
Casey B, Kollipara RK, Pozo K, and Johnson JE. (2018) Intrinsic DNA binding properties demonstrated for lineage-specifying basic helix-loop-helix transcription factors. Genome Res 28, 484-496. PMCID:PMC5880239 DOI:10.1101/gr.224360.117
Mona B*, Uruena A*, Ma, Z, Borromeo MD, Kollipara RK, Chang JC, and Johnson JE. (2017) Repression by PRDM13 is critical for generating precise neuronal identity. eLIFE 6. pii: e25787. doi: 10.7554/eLife.25787. PMCID:PMC5576485
Borromeo MD*, Savage TS*, Kollipara RK*, He M, Augustyn A, Osborne JK, Girard L, Minna JD, Gazdar AF, Cobb MH, and Johnson JE. (2016) ASCL1 and NEUROD1 reveal heterogeneity in pulmonary neuroendocrine tumors and regulate distinct genetic programs. Cell Reports 16, 1-14. (http://dx.doi.org/10.1016/j.celrep.2016.06.081)
Vue TY, Kim EJ, Parras CM, Guillemot F, and Johnson JE. (2014) Ascl1 controls the number and distribution of astrocytes and oligodendrocytes in the gray matter and white matter of the spinal cord. Development 141, 3721-3731. PMCID:PMC4197573
Borromeo MD, Meredith DM, Castro D, Chang JC, Tung KC, Guillemot F, and Johnson JE. (2014) Transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord. Development 141, 2803-2812. PMCID:PMC4197617
Meredith, DM, Borromeo, MD, Deering, TG, Casey, BH, Savage, TK, Mayer, PR, Hoang, C, Tung, KC, Kumar, M, Shen, C, Swift, GH, Macdonald, RJ, Johnson, JE (2013) Program Specificity for Ptf1a in Pancreas versus Neural Tube Development Correlates with Distinct Collaborating Cofactors and Chromatin Accessibility. Mol. Cell. Biol. 16, 3166-79.
Chang, JC, Meredith, DM, Mayer, PR, Borromeo, MD, Lai, HC, Ou, YH, Johnson, JE (2013) Prdm13 mediates the balance of inhibitory and excitatory neurons in somatosensory circuits. Dev. Cell 2, 182-95.
Lai, HC, Tiemo, JK, Roberts, R, Zoghbi, HY, and Johnson, JE (2011) In vivo neuronal subtype-specific targets of Atoh1 (Math1) in dorsal spinal cord. J Neurosci 31, 10859-10871. Supporting material (downloadable MS Excel files): Part 1, Part 2, Part 3.
Kim, EJ, Ables, JL, Dickel, LK, Eisch, AJ, and Johnson, JE (2011) Ascl1 (Mash1) defines cells with long term neurogenic potential in subgranular and subventricular zones in adult mouse brain. PLoS One 6, e18472.
Kim, EJ, Hori, K, Wyckoff, A, Dickel, LK, Koundakjian, EJ, Goodrich, LV, and Johnson, JE (2011) The spatiotemporal fate map of Neurogenin1 (Neurog1) lineages in the central nervous system. J Comp Neurol 519, 1355-1370.
Quinones, HI, Savage, TK, Battiste, J, and Johnson, JE (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, DM, Masui, T, Swift, GH, MacDonald, RJ, and Johnson, JE (2009) Multiple Transcriptional Mechanisms Control Ptf1a Levels During Neural Development Including Autoregulation by the PTF1-J Complex. Neurosci 29, 11139-11148.
Henke, RM*, Savage, TK*, Meredith, DM, Glasgow, SM, Hori, K, Dumas, J, MacDonald, RJ, and Johnson, JE (2009) Neurog2 is a Direct Downstream Target of the Ptf1a-Rbpj Transcription Complex in Dorsal Spinal Cord. Development 136, 2945-2954.
Henke, RM, Meredith, DM, Borromeo, MD, Savage, TK, and Johnson, JE (2009) Ascl1 and Neurog2 form novel complexes and regulate Delta-like3 (Dll3) expression in the neural tube. Dev. Biol. 328, 529-540.
Kim, EJ, Battiste, J, Nakagawa, Y, and Johnson, JE (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, SM, Masui, T, Henke, RM, Wildner, H, Martarelli, B, Beres, TM, Epstein, JA, Magnuson, MA, MacDonald, RJ, Birchmeier, C and Johnson, JE (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.