Publications - Salk Institute for Biological Studies

Todas las publicaciones

2026

Ozkan, A., Padmanabhan, H.K., Shipman, S.L., Azim, E., Kumar, P., Sadegh, C., Basak, A.N., Macklis, J.D. Directed differentiation of functional corticospinal-like neurons from endogenous SOX6+/NG2+ cortical progenitors. (2026) Elife. 13. DOI: 10.7554/eLife.100340

+ expandir resumen

Corticospinal neurons (CSN) centrally degenerate in amyotrophic lateral sclerosis (ALS), along with spinal motor neurons, and loss of voluntary motor function in spinal cord injury (SCI) results from damage to CSN axons. For functional regeneration of specifically affected neuronal circuitry , or for optimally informative disease modeling and/or therapeutic screening , it is important to reproduce the type or subtype of neurons involved. No such appropriate models exist with which to investigate CSN selective vulnerability and degeneration in ALS, or to investigate routes to regeneration of CSN circuitry for ALS or SCI, critically limiting the relevance of much research. Here, we identify that the HMG-domain transcription factor is expressed by a subset of NG2+ endogenous cortical progenitors in postnatal and adult cortex, and that suppresses a latent neurogenic program by repressing proneural expression by progenitors. We FACS-purify these progenitors from postnatal mouse cortex and establish a culture system to investigate their potential for directed differentiation into CSN. We then employ a multi-component construct with complementary and differentiation-sharpening transcriptional controls (activating , , while antagonizing with ). We generate corticospinal-like neurons from SOX6+/NG2+ cortical progenitors and find that these neurons differentiate with remarkable fidelity compared with corticospinal neurons in vivo. They possess appropriate morphological, molecular, transcriptomic, and electrophysiological characteristics, without characteristics of the alternate intracortical or other neuronal subtypes. We identify that these critical specifics of differentiation are not reproduced by commonly employed -driven differentiation. Neurons induced by instead exhibit aberrant multi-axon morphology and express molecular hallmarks of alternate cortical projection subtypes, often in mixed form. Together, this developmentally-based directed differentiation from cortical progenitors sets a precedent and foundation for mechanistic and therapeutic disease modeling, and toward regenerative neuronal repopulation and circuit repair.

2025

Zhang, C.Y., Yang, Y., Sirbu, A., Abe, E.T.T., Wärnberg, E., Leonardis, E.J., Aldarondo, D.E., Lee, A., Prasad, A., Foat, J., Bian, K., Park, J., Bhatt, R., Saunders, H., Nagamori, A., Thanawalla, A.R., Huang, K.W., Plum, F., Beck, H.K., Flavell, S.W., Labonte, D., Richards, B.A., Brunton, B.W., Azim, E., Ölveczky, B.P., Pereira, T.D. MIMIC-MJX: Neuromechanical Emulation of Animal Behavior. (2025) ArXiv.

+ expandir resumen

Labarta-Bajo, L., Thanawalla, A.R., Gutierrez, I.L., Lei Soe, S.M., Chick, B.Y., Andritsogianni, I., Metanat, S., Hargreaves, D.C., Kaech, S.M., Azim, E., Allen, N.J. The antiviral Interferon pathway drives astrocyte aging and motor decline. (2025) bioRxiv. DOI: 10.1101/2025.11.12.688147

+ expandir resumen

Leonardis, E., Nagamori, A., Thanawalla, A., Yang, Y., Park, J., Saunders, H., Azim, E., Pereira, T. Massively Parallel Imitation Learning of Mouse Forelimb Musculoskeletal Reaching Dynamics. (2025) ArXiv.

+ expandir resumen

Thanawalla, A.R., Wilcox, O., Rhee, E., Jiang, J., Huang, K.W., Yusufi, R., Saklaway, D., Nagamori, A., Conner, J.M., Chen, A.I., Azim, E. Cerebellar outputs for rapid directional refinement of forelimb movement. (2025) bioRxiv. DOI: 10.1101/2025.10.01.679895

+ expandir resumen

Lustig, J., Lammers, A., Kaiser, J., Patel, P., Raghu, A., Conner, J.M., Nguyen, P., Azim, E., Sahni, V. Selective Targeting of a Defined Subpopulation of Corticospinal Neurons using a Novel Klhl14-Cre Mouse Line Enables Molecular and Anatomical Investigations through Development into Maturity. (2025) eNeuro. DOI: 10.1523/ENEURO.0589-24.2025

+ expandir resumen

The corticospinal tract (CST) facilitates skilled, precise movements, which necessitates that subcerebral projection neurons (SCPN) establish segmentally specific connectivity with brainstem and spinal circuits. Developmental molecular delineation enables prospective identification of corticospinal neurons (CSN) projecting to thoraco-lumbar spinal segments; however, it remains unclear whether other SCPN subpopulations in developing sensorimotor cortex can be prospectively identified in this manner. Such molecular tools could enable investigations of SCPN circuitry with precision and specificity. During development, Kelch-like 14 () is specifically expressed by a specific SCPN subpopulation, CSN, that reside in lateral sensorimotor cortex with axonal projections exclusively to bulbar-cervical targets. In this study, we generated Klhl14-T2A-Cre knock-in mice to investigate SCPN that are during development into maturity. Using conditional anterograde and retrograde labeling in mice of either sex, we find that Klhl14-Cre is specifically expressed by CSN only at specific developmental time points. We establish conditional viral labeling in Klhl14-T2A-Cre mice as a new approach to reliably investigate CSN axon targeting and confirm that this identifies known molecular regulators of CSN axon targeting. Therefore, Klhl14-T2A-Cre mice can be used as a novel tool for identifying molecular regulators of CST axon guidance in a relatively high-throughput manner in vivo. Finally, we demonstrate that intersectional viral labeling enables precise targeting of only Klhl14-Cre+ CSN in the adult central nervous system. Together, our results establish that developmental molecular delineation of SCPN subpopulations can be used to selectively and specifically investigate their development, as well as anatomical and functional organization into maturity. The cortex connects to brainstem and spinal targets through subcerebral projection neurons (SCPN), which exhibit molecular diversity during development based on their neocortical location and axonal targets. We generated a novel Klhl14-Cre mouse line to utilize this developmental delineation and drive Cre expression in a specific SCPN subpopulation. This developmental specificity enabled investigation of 1) areal locations of Klhl14+ SCPN in mature cortex, 2) their axonal collateralization at maturity, and 3) which genes can control their axon targeting. Using intersectional tools, we can also selectively label these neurons in the adult CNS. Therefore, developmental molecular delineation of SCPN not only provides prospective identification but also enables molecular analysis during development, as well as anatomical and functional investigations in adulthood.

Yao, M., Nagamori, A., Campos Maçãs, S., Azim, E., Sharpee, T., Goulding, M., Golomb, D., Gatto, G. The spinal premotor network driving scratching flexor and extensor alternation. (2025) Cell Reports. 44(6):115845. DOI: 10.1016/j.celrep.2025.115845

+ expandir resumen

Upadhyay, A., Gradwell, M.A., Vajtay, T.J., Conner, J., Sanyal, A.A., Azadegan, C., Patel, K.R., Thackray, J.K., Bohic, M., Imai, F., Ogundare, S.O., Yoshida, Y., Abdus-Saboor, I., Azim, E., Abraira, V.E. The dorsal column nuclei scale mechanical sensitivity in naive and neuropathic pain states. (2025) Cell Reports. 44(4):115556. DOI: 10.1016/j.celrep.2025.115556

+ expandir resumen

2024

+ expandir resumen

Wu, Y., Temple, B.A., Sevilla, N., Zhang, J., Zhu, H., Zolotavin, P., Jin, Y., Duarte, D., Sanders, E., Azim, E., Nimmerjahn, A., Pfaff, S.L., Luan, L., Xie, C. Ultraflexible electrodes for recording neural activity in the mouse spinal cord during motor behavior. (2024) Cell Reports. 43(5):114199. DOI: 10.1016/j.celrep.2024.114199

+ expandir resumen

Upadhyay, A., Gradwell, M.A., Vajtay, T.J., Conner, J., Sanyal, A.A., Azadegan, C., Patel, K.R., Thackray, J.K., Bohic, M., Imai, F., Ogundare, S.O., Yoshida, Y., Abdus-Saboor, I., Azim, E., Abraira, V.E. The Dorsal Column Nuclei Scale Mechanical Sensitivity in Naive and Neuropathic Pain States. (2024) bioRxiv. DOI: 10.1101/2024.02.20.581208

+ expandir resumen

Tactile perception relies on reliable transmission and modulation of low-threshold information as it travels from the periphery to the brain. During pathological conditions, tactile stimuli can aberrantly engage nociceptive pathways leading to the perception of touch as pain, known as mechanical allodynia. Two main drivers of peripheral tactile information, low-threshold mechanoreceptors (LTMRs) and postsynaptic dorsal column neurons (PSDCs), terminate in the brainstem dorsal column nuclei (DCN). Activity within the DRG, spinal cord, and DCN have all been implicated in mediating allodynia, yet the DCN remains understudied at the cellular, circuit, and functional levels compared to the other two. Here, we show that the gracile nucleus (Gr) of the DCN mediates tactile sensitivity for low-threshold stimuli and contributes to mechanical allodynia during neuropathic pain in mice. We found that the Gr contains local inhibitory interneurons in addition to thalamus-projecting neurons, which are differentially innervated by primary afferents and spinal inputs. Functional manipulations of these distinct Gr neuronal populations resulted in bidirectional changes to tactile sensitivity, but did not affect noxious mechanical or thermal sensitivity. During neuropathic pain, silencing Gr projection neurons or activating Gr inhibitory neurons was able to reduce tactile hypersensitivity, and enhancing inhibition was able to ameliorate paw withdrawal signatures of neuropathic pain, like shaking. Collectively, these results suggest that the Gr plays a specific role in mediating hypersensitivity to low-threshold, innocuous mechanical stimuli during neuropathic pain, and that Gr activity contributes to affective, pain-associated phenotypes of mechanical allodynia. Therefore, these brainstem circuits work in tandem with traditional spinal circuits underlying allodynia, resulting in enhanced signaling of tactile stimuli in the brain during neuropathic pain.

Wirthlin, M.E., Schmid, T.A., Elie, J.E., Zhang, X., Kowalczyk, A., Redlich, R., Shvareva, V.A., Rakuljic, A., Ji, M.B., Bhat, N.S., Kaplow, I.M., Schäffer, D.E., Lawler, A.J., Wang, A.Z., Phan, B.N., Annaldasula, S., Brown, A.R., Lu, T., Lim, B.K., Azim, E., , Clark, N.L., Meyer, W.K., Pond, S.L.K., Chikina, M., Yartsev, M.M., Pfenning, A.R., Andrews, G., Armstrong, J.C., Bianchi, M., Birren, B.W., Bredemeyer, K.R., Breit, A.M., Christmas, M.J., Clawson, H., Damas, J., Di Palma, F., Diekhans, M., Dong, M.X., Eizirik, E., Fan, K., Fanter, C., Foley, N.M., Forsberg-Nilsson, K., Garcia, C.J., Gatesy, J., Gazal, S., Genereux, D.P., Goodman, L., Grimshaw, J., Halsey, M.K., Harris, A.J., Hickey, G., Hiller, M., Hindle, A.G., Hubley, R.M., Hughes, G.M., Johnson, J., Juan, D., Kaplow, I.M., Karlsson, E.K., Keough, K.C., Kirilenko, B., Koepfli, K.P., Korstian, J.M., Kowalczyk, A., Kozyrev, S.V., Lawler, A.J., Lawless, C., Lehmann, T., Levesque, D.L., Lewin, H.A., Li, X., Lind, A., Lindblad-Toh, K., Mackay-Smith, A., Marinescu, V.D., Marques-Bonet, T., Mason, V.C., Meadows, J.R.S., Meyer, W.K., Moore, J.E., Moreira, L.R., Moreno-Santillan, D.D., Morrill, K.M., Muntané, G., Murphy, W.J., Navarro, A., Nweeia, M., Ortmann, S., Osmanski, A., Paten, B., Paulat, N.S., Pfenning, A.R., Phan, B.N., Pollard, K.S., Pratt, H.E., Ray, D.A., Reilly, S.K., Rosen, J.R., Ruf, I., Ryan, L., Ryder, O.A., Sabeti, P.C., Schäffer, D.E., Serres, A., Shapiro, B., Smit, A.F.A., Springer, M., Srinivasan, C., Steiner, C., Storer, J.M., Sullivan, K.A.M., Sullivan, P.F., Sundström, E., Supple, M.A., Swofford, R., Talbot, J.E., Teeling, E., Turner-Maier, J., Valenzuela, A., Wagner, F., Wallerman, O., Wang, C., Wang, J., Weng, Z., Wilder, A.P., Wirthlin, M.E., Xue, J.R., Zhang, X. Vocal learning-associated convergent evolution in mammalian proteins and regulatory elements. (2024) Ciencia.:eabn3263 DOI: 10.1126/science.abn3263

+ expandir resumen

2023

Chung, B., Zia, M., Thomas, K.A., Michaels, J.A., Jacob, A., Pack, A., Williams, M.J., Nagapudi, K., Teng, L.H., Arrambide, E., Ouellette, L., Oey, N., Gibbs, R., Anschutz, P., Lu, J., Wu, Y., Kashefi, M., Oya, T., Kersten, R., Mosberger, A.C., O'Connell, S., Wang, R., Marques, H., Mendes, A.R., Lenschow, C., Kondakath, G., Kim, J.J., Olson, W., Quinn, K.N., Perkins, P., Gatto, G., Thanawalla, A., Coltman, S., Kim, T., Smith, T., Binder-Markey, B., Zaback, M., Thompson, C.K., Giszter, S., Person, A., Goulding, M., Azim, E., Thakor, N., O'Connor, D., Trimmer, B., Lima, S.Q., Carey, M.R., Pandarinath, C., Costa, R.M., Pruszynski, J.A., Bakir, M., Sober, S.J. Myomatrix arrays for high-definition muscle recording. (2023) Elife. 12. DOI: 10.7554/eLife.88551

+ expandir resumen

Butler, D.J., Keim, A.P., Ray, S., Azim, E. Large-scale capture of hidden fluorescent labels for training generalizable markerless motion capture models. (2023) Nature Communications. 14(1):5866. DOI: 10.1038/s41467-023-41565-3

+ expandir resumen

2022

Huang, K.W., Azim, E. Neurons that promote recovery from paralysis identified. (2022) Naturaleza. 611(7936):452-453. DOI: 10.1038/d41586-022-02234-5

2021

Low, A.Y.T., Goldstein, N., Gaunt, J.R., Huang, K.P., Zainolabidin, N., Yip, A.K.K., Carty, J.R.E., Choi, J.Y., Miller, A.M., Ho, H.S.T., Lenherr, C., Baltar, N., Azim, E., Sessions, O.M., Ch'ng, T.H., Bruce, A.S., Martin, L.E., Halko, M.A., Brady, R.O., Holsen, L.M., Alhadeff, A.L., Chen, A.I., Betley, J.N. Reverse-translational identification of a cerebellar satiation network. (2021) Naturaleza. DOI: 10.1038/s41586-021-04143-5

+ expandir resumen

Conner, J.M., Bohannon, A., Igarashi, M., Taniguchi, J., Baltar, N., Azim, E. Modulation of tactile feedback for the execution of dexterous movement. [Pubmed] (2021) Ciencia. 374(6565):316-323. DOI: 10.1126/science.abh1123

+ expandir resumen

Karashchuk, P., Rupp, K.L., Dickinson, E.S., Walling-Bell, S., Sanders, E., Azim, E., Brunton, B.W., Tuthill, J.C. Anipose: A toolkit for robust markerless 3D pose estimation. (2021) Cell Reports. 36(13):109730. DOI: 10.1016/j.celrep.2021.109730

+ expandir resumen

2020

Thanawalla, A.R., Chen, A.I., Azim, E. The cerebellar nuclei and dexterous limb movements. (2020) Neuroscience. DOI: 10.1016/j.neuroscience.2020.06.046

+ expandir resumen

2019

Azim, E., Seki, K. Gain control in the sensorimotor system. (2019) Current Opinion in Physiology. 8:177-187. DOI: 10.1016/j.cophys.2019.03.005

+ expandir resumen

2018

Tuthill, J.C., Azim, E. Proprioception. (2018) Current Biology. 28(5):R194-R203. DOI: 10.1016/j.cub.2018.01.064

+ expandir resumen

2016

Kishi, N., MacDonald, J.L., Ye, J., Molyneaux, B.J., Azim, E., Macklis, J.D. Reduction of aberrant NF-κB signalling ameliorates Rett syndrome phenotypes in Mecp2-null mice. (2016) Nature Communications. 7:10520. DOI: 10.1038/ncomms10520

+ expandir resumen

2015

Azim, E., Alstermark, B. Skilled forelimb movements and internal copy motor circuits. (2015) Current Opinion in Neurobiology. 33:16-24. DOI: 10.1016/j.conb.2014.12.009

+ expandir resumen

Jiang, J., Azim, E., Ekerot, C.F., Alstermark, B. Direct and indirect spino-cerebellar pathways: shared ideas but different functions in motor control. (2015) Frontiers in Computational Neuroscience. 9:75. DOI: 10.3389/fncom.2015.00075

+ expandir resumen

2014

Azim, E. Neuroscience. Shortcuts and checkpoints on the road to skilled movement. (2014) Ciencia. 346(6209):554-5. DOI: 10.1126/science.1260778

Fink, A.J., Croce, K.R., Huang, Z.J., Abbott, L.F., Jessell, T.M., Azim, E. Presynaptic inhibition of spinal sensory feedback ensures smooth movement. (2014) Naturaleza. 509(7498):43-8. DOI: 10.1038/nature13276

+ expandir resumen

Azim, E., Jiang, J., Alstermark, B., Jessell, T.M. Skilled reaching relies on a V2a propriospinal internal copy circuit. (2014) Naturaleza. 508(7496):357-63. DOI: 10.1038/nature13021

+ expandir resumen

Azim, E., Fink, A.J., Jessell, T.M. Internal and External Feedback Circuits for Skilled Forelimb Movement. (2014) Cold Spring Harbor Symposia on Quantitative Biology. 79:81-92. DOI: 10.1101/sqb.2014.79.024786

+ expandir resumen

2013

Miri, A., Azim, E., Jessell, T.M. Edging toward entelechy in motor control. (2013) Neuron. 80(3):827-34. DOI: 10.1016/j.neuron.2013.10.049

+ expandir resumen

Cederquist, G.Y., Azim, E., Shnider, S.J., Padmanabhan, H., Macklis, J.D. Lmo4 establishes rostral motor cortex projection neuron subtype diversity. (2013) Journal of Neuroscience. 33(15):6321-32. DOI: 10.1523/JNEUROSCI.5140-12.2013

+ expandir resumen

Azim, E. (2013) Patterning and Cell Type Specification in the Developing CNS and PNS Comprehensive Developmental Neuroscience. DOI: https://doi.org/10.1016/B978-0-12-397265-1.00098-8

+ expandir resumen

2009

Azim, E., Jabaudon, D., Fame, R.M., Macklis, J.D. SOX6 controls dorsal progenitor identity and interneuron diversity during neocortical development. (2009) Nature Neuroscience. 12(10):1238-47. DOI: 10.1038/nn.2387

+ expandir resumen

Azim, E., Shnider, S.J., Cederquist, G.Y., Sohur, U.S., Macklis, J.D. Lmo4 and Clim1 progressively delineate cortical projection neuron subtypes during development. (2009) Cereb. Cortex. 19 Suppl 1:i62-9. DOI: 10.1093/cercor/bhp030

+ expandir resumen

2008

Lai, T., Jabaudon, D., Molyneaux, B.J., Azim, E., Arlotta, P., Menezes, J.R., Macklis, J.D. SOX5 controls the sequential generation of distinct corticofugal neuron subtypes. (2008) Neuron. 57(2):232-47. DOI: 10.1016/j.neuron.2007.12.023

+ expandir resumen

2005

Azim, E., Mobbs, D., Jo, B., Menon, V., Reiss, A.L. Sex differences in brain activation elicited by humor. (2005) Actas de la Academia Nacional de Ciencias de los Estados Unidos de América. 102(45):16496-501. DOI: 10.1073/pnas.0408456102

+ expandir resumen

Mobbs, D., Hagan, C.C., Azim, E., Menon, V., Reiss, A.L. Personality predicts activity in reward and emotional regions associated with humor. (2005) Actas de la Academia Nacional de Ciencias de los Estados Unidos de América. 102(45):16502-6. DOI: 10.1073/pnas.0408457102

+ expandir resumen

2003

Mobbs, D., Greicius, M.D., Abddel-Azim, E., Menon, V., Reiss, A.L. Humor modulates the mesolimbic reward centers. (2003) Neuron. 40(5):1041-8. DOI: 10.1016/s0896-6273(03)00751-7

+ expandir resumen

Eiman Azim, doctora

Instituto Salk de Estudios Biológicos - Publicaciones

Todas las publicaciones

2026

2025

2024

2023

2022

2021

2020

2019

2018

2016

2015

2014

2013

2009

2008

2005

2003

Apoya la Investigación Salk

Educación

Afiliaciones

Premios y distinciones

Perfil

Características

Sitio web

Contacto