Development, Genetics, Genomics, Neurobiology, Regulation of Gene Expression
Regulation of temporal patterning in neural progenitors and subsequent generation of neural diversity
Generation of neural diversity is a key question in developmental neurobiology. Studies in both vertebrates and Drosophila have shown that neural progenitors are temporally patterned to generate different neural types in a defined order. We use the Drosophila medulla (the first color-information processing center) to address this question. Through an antibody screen, we identified a large set of transcription factors expressed in the developing medulla, and five of them, Homothorax (Hth), Eyeless (Ey), Sloppy paired 1 and 2 (Slp), Dichaete (D) and Tailless (Tll), are expressed sequentially in neural progenitors called neuroblasts as they age. These temporally-expressed transcription factors are required for sequential generation of different neural types. Cross-regulation between these transcription factors is required but not sufficient for temporal transitions, suggesting additional mechanism is required.
My lab’s goal is to elucidate the molecular mechanism controlling the sequential temporal transitions in medulla neuroblasts to generate different neural types, using both genetics and genomics approaches. In a genomics approach, we compare the transcriptome profiles of medulla neuroblasts as they transit through different temporal stages using the five transcription factors as markers. In parallel, we use genetic analysis to identify the molecular players and elucidate the molecular clock. The integrated approaches are also used in our investigation of how the sequential expression of transcription factors in neuroblasts generates neural diversity. Our research will shed light on the neurogenesis of a complex adult neural structure, as well as on the general mechanism of temporal patterning of neural progenitors.
B.S., Beijing Medical University, China
Ph.D., Northwestern University
Postdoc., New York University
Awards and Honors
Robert Leet and Clara Guthrie Patterson Trust Postdoctoral Fellowship Program in Brain Circuitry, The Medical Foundation (2008-2010)
Additional Campus Affiliations
Associate Professor, Cell and Developmental Biology
Affiliate, Carl R. Woese Institute for Genomic Biology
Yu Zhang, Scott Lowe, Andrew Z. Ding and Xin Li (2023). “Notch-dependent binary fate choice regulates the Netrin pathway to control axon guidance of Drosophila visual projection neurons.” Cell Reports. 42 (3): 112143, https://doi.org/10.1016/j.celrep.2023.112143.
Yu Zhang, Scott Lowe, Andrew Z. Ding and Xin Li (2023). “Axon targeting of Drosophila medulla projection neurons requires diffusible Netrin and is coordinated with neuroblast temporal patterning”. Cell Reports. 42(3):112144. doi: 10.1016/j.celrep.2023.112144.
Alokananda Ray and Xin Li (2022), “A Notch-dependent transcriptional mechanism controls expression of temporal patterning factors in Drosophila medulla”. eLife. 11:e75879. https://doi.org/10.7554/eLife.75879.
Hailun Zhu, Sihai Dave Zhao, Alokananda Ray, Yu Zhang, and Xin Li (2022), "A comprehensive temporal patterning gene network in Drosophila medulla neuroblasts revealed by single-cell RNA sequencing", Nature Communications. 13, 1247 (2022). https://doi.org/10.1038/s41467-022-28915-3.
Editorial: Xin Li and Mubarak Hussain Syed (2022). “Time, Space, and Diversity”. for Special Issue on “Temporal Patterning in the CNS”, Seminars in Cell & Developmental Biology. Sep10;S1084-9521(22)00264-6, doi: 10.1016/j.semcdb.2022.09.002.
Alokananda Ray, Hailun Zhu, Andrew Ding and Xin Li. "Transcriptional and epigenetic regulation of temporal patterning in neural progenitors". Developmental Biology. 481, 116–128 (2022). PMID: 34666024.
Vamsikrishna G. Naidu, Yu Zhang, Scott Lowe, Alokananda Ray, Hailun Zhu and Xin Li (2020) “Temporal progression of Drosophila medulla neuroblasts generates the transcription factor combination to control T1 neuron morphogenesis.” Developmental Biology. 464 (1): 35-44. doi:https://doi.org/10.1016/j.ydbio.2020.05.005
Filipe Pinto-Teixeira, Clara Koo, Anthony Michael Rossi, Nathalie Neriec, Claire Bertet, Xin Li, Alberto Del-Valle-Rodriguez, and Claude Desplan (2018), “Development of Concurrent Retinotopic Maps in the Fly Motion Detection Circuit.” Cell. 173(2):485-498.e11. doi: 10.1016/j.cell.2018.02.053.
Ted Erclik*, Xin Li*, Maximilien Courgeon*, Claire Bertet, Zhenqing Chen, Ryan Baumert, June Ng, Clara Koo, Urfa Arain, Rudy Behnia, Alberto Del Valle Rodriguez, Lionel Senderowicz, Nicolas Negre, Kevin P. White & Claude Desplan (2017) “Integration of temporal and spatial patterning generates neural diversity.” Nature, 541, 365–370. *Equal contribution.
Claire Bertet, Xin Li, Ted Erclik, Matthieu Cavey, Brent Wells and Claude Desplan (2014) “Temporal patterning of neuroblasts controls Notch-mediated cell survival through regulation of Hid or Reaper.” Cell. 158 (5):1173-86.
Xin Li, Zhenqing Chen and Claude Desplan (2013) “Temporal patterning of neural progenitors in Drosophila”, Current Topics in Developmental Biology, 105:69-96.
Xin Li*, Ted Erclik*, Claire Bertet, Zhenqing Chen, Roumen Voutev, Srinidhi Venkatesh, Javier Morante, Arzu Celik and Claude Desplan (2013) “Temporal patterning of Drosophila medulla neuroblasts controls neural fates.” * Equal contribution. Nature, 498(7455):456-62.
Xin Li*, Justin J. Cassidy*, Catherine A. Reinke, Stephen Fischboeck and Richard W. Carthew (2009) “A microRNA imparts robustness against environmental fluctuation during development.” Cell 137, 273–282. * Equal contribution.
Xin Li and Richard W. Carthew (2005) “A microRNA mediates EGF receptor signaling and promotes photoreceptor differentiation in the Drosophila eye.” Cell 123, 1267-1277.
Zhu, H., Zhao, S. D., Ray, A., Zhang, Y., & Li, X. (2022). A comprehensive temporal patterning gene network in Drosophila medulla neuroblasts revealed by single-cell RNA sequencing. Nature communications, 13(1), Article 1247. https://doi.org/10.1038/s41467-022-28915-3
Naidu, V. G., Zhang, Y., Lowe, S., Ray, A., Zhu, H., & Li, X. (2020). Temporal progression of Drosophila medulla neuroblasts generates the transcription factor combination to control T1 neuron morphogenesis. Developmental Biology, 464(1), 35-44. https://doi.org/10.1016/j.ydbio.2020.05.005
Pinto-Teixeira, F., Koo, C., Rossi, A. M., Neriec, N., Bertet, C., Li, X., Del-Valle-Rodriguez, A., & Desplan, C. (2018). Development of Concurrent Retinotopic Maps in the Fly Motion Detection Circuit. Cell, 173(2), 485-498.e11. https://doi.org/10.1016/j.cell.2018.02.053
Erclik, T., Li, X., Courgeon, M., Bertet, C., Chen, Z., Baumert, R., Ng, J., Koo, C., Arain, U., Behnia, R., Del Valle Rodriguez, A., Senderowicz, L., Negre, N., White, K. P., & Desplan, C. (2017). Integration of temporal and spatial patterning generates neural diversity. Nature, 541(7637), 365-370. https://doi.org/10.1038/nature20794
Chen, Z., Del Valle Rodriguez, A., Li, X., Erclik, T., Fernandes, V. M., & Desplan, C. (2016). A Unique Class of Neural Progenitors in the Drosophila Optic Lobe Generates Both Migrating Neurons and Glia. Cell Reports, 15(4), 774-786. https://doi.org/10.1016/j.celrep.2016.03.061