Yasushi Nakagawa, MD, PhD

Development of the mammalian forebrain

Our current interests include the intrinsic mechanisms of thalamic development and the roles of thalamic input in neocortical development. We extensively use mouse genetics and in vivo gene delivery into developing embryos. Efforts in our lab are directed at two major goals:

1. We are trying to understand how the developing thalamus produces different neuronal populations that later form distinct nuclei. We have characterized the spatial and temporal heterogeneity of progenitor cell populations in the thalamus. We are now trying to reveal molecular mechanisms that regulate such heterogeneity. Some of our recent works have determined the roles of Sonic hedgehog and Wnt signaling in this process, and how these intrinsic patterning mechanisms eventually affect the formation of thalamic nuclei in mice.
2. We are trying to examine the roles of thalamocortical projections in the formation of functionally and anatomically distinct sensory areas in neocortex. To dissect local patterning mechanisms operating within neocortex and extrinsic mechanisms conveyed by the thalamic input, we are analyzing mutant mice in which certain thalamic nuclei are specifically alerted in size or the entire thalamocortical projections are compromised. Using these mice, we will determine the precise roles of thalamic afferents in neocortical development.

Larsen, R, Proue, A, Scott, EP, Christiansen, M & Nakagawa, Y 2019, 'The thalamus regulates retinoic acid signaling and development of parvalbumin interneurons in postnatal mouse prefrontal cortex' eNeuro, vol. 6, no. 1, e0018-19.2019. https://doi.org/10.1523/ENEURO.0018-19.2019

Wong, SZH, Scott, EP, Mu, W, Guo, X, Borgenheimer, E, Freeman, M, Ming, GL, Wu, QF, Song, H & Nakagawa, Y 2018, 'In vivo clonal analysis reveals spatiotemporal regulation of thalamic nucleogenesis' PLoS Biology, vol. 16, no. 4, e2005211. https://doi.org/10.1371/journal.pbio.2005211

De Clercq, S, Keruzore, M, Desmaris, E, Pollart, C, Assimacopoulos, S, Preillon, J, Ascenzo, S, Matson, CK, Lee, M, Nan, X, Li, M, Nakagawa, Y, Hochepied, T, Zarkower, D, Grove, EA & Bellefroid, EJ 2018, 'DMRT5 Together with DMRT3 Directly Controls Hippocampus Development and Neocortical Area Map Formation' Cerebral Cortex, vol. 28, no. 2, pp. 493-509. https://doi.org/10.1093/cercor/bhw384

Zechel, S, Nakagawa, Y & Ibáñez, CF 2016, 'Thalamo-cortical axons regulate the radial dispersion of neocortical GABAergic interneurons' eLife, vol. 5, no. DECEMBER2016, e20770. https://doi.org/10.7554/eLife.20770

Sokolowski, K, Tran, T, Esumi, S, Kamal, Y, Oboti, L, Lischinsky, J, Goodrich, M, Lam, A, Carter, M, Nakagawa, Y & Corbin, JG 2016, 'Molecular and behavioral profiling of Dbx1-derived neurons in the arcuate, lateral and ventromedial hypothalamic nuclei' Neural Development, vol. 11, no. 1, 12. https://doi.org/10.1186/s13064-016-0067-9

Saulnier, A, Keruzore, M, De Clercq, S, Bar, I, Moers, V, Magnani, D, Walcher, T, Filippis, C, Kricha, S, Parlier, D, Viviani, L, Matson, CK, Nakagawa, Y, Theil, T, Götz, M, Mallamaci, A, Marine, JC, Zarkower, D & Bellefroid, EJ 2013, 'The doublesex homolog Dmrt5 is required for the development of the caudomedial cerebral cortex in mammals' Cerebral Cortex, vol. 23, no. 11, pp. 2552-2567. https://doi.org/10.1093/cercor/bhs234

Vue, TY, Lee, M, Tan, YE, Werkhoven, Z, Wang, L & Nakagawa, Y 2013, 'Thalamic control of neocortical area formation in mice' Journal of Neuroscience, vol. 33, no. 19, pp. 8442-8453. https://doi.org/10.1523/JNEUROSCI.5786-12.2013

Chou, SJ, Babot, Z, Leingar?tner, A, Studer, M, Nakagawa, Y & O'Leary, DDM 2013, 'Geniculocortical input drives genetic distinctions between primary and higher-order visual areas' Science, vol. 340, no. 6137, pp. 1239-1242. https://doi.org/10.1126/science.1232806

Nakagawa, Y & Shimogori, T 2012, 'Diversity of thalamic progenitor cells and postmitotic neurons' European Journal of Neuroscience, vol. 35, no. 10, pp. 1554-1562. https://doi.org/10.1111/j.1460-9568.2012.08089.x

Bluske, KK, Vue, TY, Kawakami, Y, Taketo, MM, Yoshikawa, K, Johnson, JE & Nakagawa, Y 2012, '?-Catenin signaling specifies progenitor cell identity in parallel with Shh signaling in the developing mammalian thalamus.' Development (Cambridge, England), vol. 139, no. 15, pp. 2692-2702. https://doi.org/10.1242/dev.072314