Generation and Regeneration of Bilateral Neural Circuits

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Lines of investigation

The precise trajectory of different neuronal types during development is essential for the proper formation of functional circuits. We investigate the molecular and cellular mechanisms underlying axon pathfinding, focusing on how neurons interpret extracellular cues, make directional choices, and integrate into neural networks.

Our research explores the role of intrinsic neuronal factors, transcriptional and epigenetic regulators, and extrinsic signals that shape axonal navigation and define specific neuronal trajectories.A major focus of our work is deciphering how signaling pathways—particularly those involved in cytoskeletal remodeling and axon guidance—contribute to both developmental and regenerative processes.

By bridging developmental neuroscience with regenerative medicine, we aim to develop innovative therapeutic approaches to restore neuronal connectivity in the injured CNS.

Using a combination of in vivo and in vitro models, advanced imaging techniques, and molecular biology tools, we dissect the intricate signaling networks that control axon guidance and circuit assembly. Ultimately, our research seeks to pave the way for future clinical applications that could benefit patients with neurodegenerative diseases or CNS injuries.

Representative Publications

ARID1A-BAF coordinates ZIC2 genomic occupancy for epithelial-to-mesenchymal transition in cranial neural crest specification. Barnada SM, Giner de Gracia A, Morenilla-Palao C, López-Cascales MT, Scopa C, Waltrich FJ Jr, Mikkers HMM, Cicardi ME, Karlin J, Trotti D, Peterson KA, Brugmann SA, Santen GWE, McMahon SB, Herrera E*, Trizzino M*. Am J Hum Genet. 2024 111 (10) :2232-2252 https://doi.org/10.1016/j.ajhg.2024.07.022
Proper Frequency of Perinatal Retinal Waves Is Essential for the Precise Wiring of Visual Axons in Nonimage-Forming Nuclei. Negueruela S, Morenilla-Palao C, Herrera M, Coca Y, Florez-Paz D, López-Cascales MT, Gomis A, Herrera E*. J Neurosci. 2024 44 (40): e1408232024 https://doi.org/10.1523/JNEUROSCI.1408-23.2024
Development of the Binocular Circuit. Herrera E, Chédotal A, Mason C. Annual Review of Neuroscience. 2024 47: 303-322 (Review) https://doi.org/10.1146/annurev-neuro-111020-093230
A Retino-retinal Projection Guided by Unc5c Emerged in Species with Retinal Waves Murcia-Belmonte V, Coca Y, Vegar C, Negueruela S, de Juan Romero C, Valiño AJ, Sala S, DaSilva R, Kania A, Borrell V, Martinez LM, Erskine L, Herrera E Current Biology 2019 29(7):1149 https://doi.org/10.1016/j.cub.2019.02.052
The peripheral eye: A neurogenic area with potential to treat retinal pathologies? Fernandez-Nogales M, Murcia-Belmonte V, Chen HY, Herrera E Progress in Retinal and Eye Research 2019 68:110 https://doi.org/10.1016/j.preteyeres.2018.09.001
The Ciliary Margin Zone of the Mammalian Retina Generates Retinal Ganglion Cells Marcucci F, Murcia-Belmonte V, Wang Q, Coca Y, Ferreiro-Galve S, Kuwajima T, Khalid S, Ross ME, Mason C, Herrera E Cell Rep 2016 17(12):3153 https://doi.org/10.1016/j.celrep.2016.11.016
Zic2-Dependent Axon Midline Avoidance Controls the Formation of Major Ipsilateral Tracts in the CNS Escalante A, Murillo B, Morenilla-Palao C, Klar A, Herrera E Neuron 2013 80(6):1392 https://doi.org/10.1016/j.neuron.2013.10.007

Group leader

Eloísa Herrera González de Molina Profesor de Investigación CSIC

Staff Scientist

Mª Cruz Morenilla Palao Profesor Doctor UMH

Tenure-Track Scientist

Augusto Escalante Rodríguez Investigador Ramón y Cajal UMH

Postdoctoral Researcher

Marta Fernández Nogales

Verónica Murcia Belmonte

Predoctoral Researcher

Leonor Filipe Silva Dos Reis Novais

Patricia Ordoño Carramiñana

Isabel Pérez Ferrer

Technical personnel

Yaiza Lisset Coca Ulloa

Macarena Herrera González de la Higuera

Administration personnel

Vasiliki Katsomaliari Asistente laboratorio

EphA4 mediates ephrinB1-dependent adhesion in retinal ganglion cells. Murcia-Belmonte V, Chauvin G, Coca Y, Escalante A, Klein R, Herrera E. Journal of Neuroscience. 2025 45(4): e0043242024 https://doi.org/10.1523/JNEUROSCI.0043-24.2024
Analysis of Microtubule Polymerization During Axon Outgrowth Using Fluorescently Labeled Microtubule Plus-End Tracking Proteins. Pérez-Ferrer I., Sánchez-Huertas C. Book: "Neuronal Morphogenesis" 2024 chapter: pp 235-249 https://10.1007/978-1-0716-3969-6
Transplantation of dorsal root ganglia overexpressing the NaChBac sodium channel improves locomotion after complete SCI. Sonia Hingorani, Guillem Paniagua Soriano, Carlos Sánchez Huertas, Eva María Villalba Riquelme , Eric López Mocholi, Beatriz Martínez Rojas, Ana Alastrué Agudo, Sebastián Dupraz, Antonio Vicente Ferrer Montiel, Victoria Moreno Manzano. Molecular Therapy. 2024 32(6): p1739-1759 https://doi.org/10.1016/j.ymthe.2024.03.038
Development of the Binocular Circuit. Herrera E, Chédotal A, Mason C. Annual Review of Neuroscience. 2024 47: 303-322 (Review) https://doi.org/10.1146/annurev-neuro-111020-093230
Proper Frequency of Perinatal Retinal Waves Is Essential for the Precise Wiring of Visual Axons in Nonimage-Forming Nuclei. Negueruela S, Morenilla-Palao C, Herrera M, Coca Y, Florez-Paz D, López-Cascales MT, Gomis A, Herrera E*. J Neurosci. 2024 44 (40): e1408232024 https://doi.org/10.1523/JNEUROSCI.1408-23.2024
ARID1A-BAF coordinates ZIC2 genomic occupancy for epithelial-to-mesenchymal transition in cranial neural crest specification. Barnada SM, Giner de Gracia A, Morenilla-Palao C, López-Cascales MT, Scopa C, Waltrich FJ Jr, Mikkers HMM, Cicardi ME, Karlin J, Trotti D, Peterson KA, Brugmann SA, Santen GWE, McMahon SB, Herrera E*, Trizzino M*. Am J Hum Genet. 2024 111 (10) :2232-2252 https://doi.org/10.1016/j.ajhg.2024.07.022
Editorial – Friedrich Bonhoeffer (1932-2021). Klein, R., Wilkinson, D., Herrera, E. Neuroscience 2023 508: 1-2 https://doi.org/10.1016/j.neuroscience.2022.11.019
CyclinD2-mediated regulation of neurogenic output from the retinal ciliary margin is perturbed in albinism. Slavi, N., Balasubramanian, R., Lee, M.A., Liapin, M., Oaks-Leaf, R., Peregrin, J., Potenski, A., Troy, C.M., Ross, M.E., Herrera, E., Kosmidis, S., John, S.W.M., Mason, C.A. Neuron 2023 111(1): 49-64.e5 https://doi.org/10.1016/j.neuron.2022.10.025
Transcriptional Control of Axon Guidance at Midline Structures. Herrera E, Escalante A Front Cell Dev Biol. 2022 10: art 840005 https://doi.org/10.3389/fcell.2022.840005
CBP and p300 Jointly Maintain Neural Progenitor Viability but Play Unique Roles in the Differentiation of Neural Lineages. González-Martínez, R., Márquez-Galera, A., Del Blanco, B., López-Atalaya, J.P., Barco, A., Herrera, E. Cells 2022 11(24): 4118 https://doi.org/10.3390/cells11244118
Multiomic Analysis of Neurons with Divergent Projection Patterns Identifies Novel Regulators of Axon Pathfinding Fernández-Nogales, M., López-Cascales, M.T., Murcia-Belmonte, V., Escalante, A., Fernández-Albert, J., Muñoz-Viana, R., Barco, A., Herrera, E. Advanced Science 2022 9 (29): art. 2200615 https://doi.org/10.1002/advs.202200615
Bilateral visual projections exist in non-teleost bony fish and predate the emergence of tetrapods Vigouroux RJ, Duroure K, Vougny J, Albadri S, Kozulin P, Herrera E, Nguyen-Ba-Charvet K, Braasch I, Suárez R, Del Bene F, Chédotal A Science 2021 372(6538):150 https://doi.org/10.1126/science.abe7790
Non-productive angiogenesis disassembles ASS plaque-associated blood vessels Alvarez-Vergara MI, Rosales-Nieves AE, March-Diaz R, Rodriguez-Perinan G, Lara-Ureña N, Ortega-de San Luis C, Sanchez-Garcia MA, Martin-Bornez M, Gómez-Gálvez P, Vicente-Munuera P, Fernandez-Gomez B, Marchena MA, Bullones-Bolanos AS, Davila JC, Gonzalez-Martinez R, Trillo-Contreras JL, Sanchez-Hidalgo AC, Del Toro R, Scholl FG, Herrera E, Trepel M, Körbelin J, Escudero LM, Villadiego J, Echevarria M, de Castro F, Gutierrez A, Rabano A, Vitorica J, Pascual A Nat Commun 2021 12(1):3098 https://doi.org/10.1038/s41467-021-23337-z
With the Permission of Microtubules: An Updated Overview on Microtubule Function During Axon Pathfinding Sánchez-Huertas C, Herrera E Front Mol Neurosci 2021 14:759404 https://doi.org/10.3389/fnmol.2021.759404
A Zic2-regulated switch in a noncanonical Wnt/betacatenin pathway is essential for the formation of bilateral circuits Morenilla-Palao C, López-Cascales MT, López-Atalaya JP, Baeza D, Calvo-Díaz L, Barco A, Herrera E Sci Adv 2020 6(46):eaaz8797 https://doi.org/10.1126/sciadv.aaz8797
New techniques for studying neurodevelopment Escalante A, González-Martínez R, Herrera E Fac Rev 2020 9:17 https://doi.org/10.12703/r/9-17
A Retino-retinal Projection Guided by Unc5c Emerged in Species with Retinal Waves Murcia-Belmonte V, Coca Y, Vegar C, Negueruela S, de Juan Romero C, Valiño AJ, Sala S, DaSilva R, Kania A, Borrell V, Martinez LM, Erskine L, Herrera E Current Biology 2019 29(7):1149 https://doi.org/10.1016/j.cub.2019.02.052
Cranial Pair II: The Optic Nerves Herrera E, Agudo-Barriuso M, Murcia-Belmonte V Anatomical Record 2019 302(3):428 https://doi.org/10.1002/ar.23922
Guidance of retinal axons in mammals Herrera E, Erskine L, Morenilla-Palao C Semin Cell Dev Biol 2019 85:48 https://doi.org/10.1016/j.semcdb.2017.11.027
The peripheral eye: A neurogenic area with potential to treat retinal pathologies? Fernandez-Nogales M, Murcia-Belmonte V, Chen HY, Herrera E Progress in Retinal and Eye Research 2019 68:110 https://doi.org/10.1016/j.preteyeres.2018.09.001
Wiring the Binocular Visual Pathways Murcia-Belmonte V, Erskine L Int Journal of Molecular Sciences 2019 20(13):3282 https://doi.org/10.3390/ijms20133282
Shh-ushing Midline Crossing through Remote Protein Transport Herrera E, Sitko AA, Bovolenta P Neuron 2018 97(2):256 https://doi.org/10.1016/j.neuron.2018.01.001
Rodent Zic Genes in Neural Network Wiring Herrera, Eloisa ZIC FAMILY: EVOLUTION, DEVELOPMENT AND DISEASE 2018 1046:209 https://doi.org/10.1007/978-981-10-7311-3_11
Roof Plate-Derived Radial Glial-like Cells Support Developmental Growth of Rapidly Adapting Mechanoreceptor Ascending Axons Kridsada K, Niu J, Haldipur P, Wang Z, Ding L, Li JJ, Lindgren AG, Herrera E, Thomas GM, Chizhikov VV, Millen KJ, Luo W Cell Rep 2018 23(10):2928 https://doi.org/10.1016/j.celrep.2018.05.025
Zic-Proteins Are Repressors of Dopaminergic Forebrain Fate in Mice and C elegans Tiveron MC, Beclin C, Murgan S, Wild S, Angelova A, Marc J, Core N, de Chevigny A, Herrera E, Bosio A, Bertrand V, Cremer H J Neurosci 2017 37(44):10611 https://doi.org/10.1523/JNEUROSCI.3888-16.2017
Time-Lapse Imaging and Cell Tracking of Migrating Cells in Slices and Flattened Telencephalic Vesicles Murcia-Belmonte V, Exposito G, Herrera E Curr Protoc Neurosci 2017 79:3.31.1 https://doi.org/10.1002/cpns.24
Genetic maps and patterns of cerebral cortex folding de Juan Romero C, Borrell V Curr Opin Cell Biol 2017 49:31 https://doi.org/10.1016/j.ceb.2017.11.009
Cerebellar Transplantation: A Potential Model to Study Repair and Development of Neurons and Circuits in the Cerebellum Sotelo, C Contemporary Clinical Neuroscience 2017 21:465 https://doi.org/10.1007/978-3-319-59749-2_22
The Ciliary Margin Zone of the Mammalian Retina Generates Retinal Ganglion Cells Marcucci F, Murcia-Belmonte V, Wang Q, Coca Y, Ferreiro-Galve S, Kuwajima T, Khalid S, Ross ME, Mason C, Herrera E Cell Rep 2016 17(12):3153 https://doi.org/10.1016/j.celrep.2016.11.016
Zic2 Controls the Migration of Specific Neuronal Populations in the Developing Forebrain Murillo B, Ruiz-Reig N, Herrera M, Fairen A, Herrera E J Neurosci 2015 35(32):11266 https://doi.org/10.1523/JNEUROSCI.0779-15.2015
Fine-tuned SRF activity controls asymmetrical neuronal outgrowth: implications for cortical migration, neural tissue lamination and circuit assembly Scandaglia M, Benito E, Morenilla-Palao C, Fiorenza F, del Blanco B, Coca Y, Herrera E, Barco A Sci Rep 2015 5:17470 https://doi.org/10.1038/srep17470
Connecting the Retina to the Brain Erskine L, Herrera E ASN Neuro 2014 6(6):1759091414562107 https://doi.org/10.1177/1759091414562107
Uncoupling of EphA/ephrinA signaling and spontaneous activity in neural circuit wiring Benjumeda I, Escalante A, Law C, Morales D, Chauvin G, Muca G, Coca Y, Lopez-Bendito G, Kania A, Martinez-Otero L, Herrera E J Neurosci 2013 33(46):18208 https://doi.org/10.1523/JNEUROSCI.1931-13.2013
Zic2-Dependent Axon Midline Avoidance Controls the Formation of Major Ipsilateral Tracts in the CNS Escalante A, Murillo B, Morenilla-Palao C, Klar A, Herrera E Neuron 2013 80(6):1392 https://doi.org/10.1016/j.neuron.2013.10.007
Shh/Boc signaling is required for sustained generation of ipsilateral projecting ganglion cells in the mouse retina Sanchez-Arrones L, Nieto-Lopez F, Sanchez-Camacho C, Carreres MI, Herrera E, Okada A, Bovolenta P J Neurosci 2013 33(20):8596 https://doi.org/10.1523/JNEUROSCI.2083-12.2013
Transcription Factor Foxd1 Is Required for the Specification of the Temporal Retina in Mammals Carreres MI, Escalante A, Murillo B, Chauvin G, Gaspar P, Vegar C, Herrera E J Neurosci 2011 31(15):5673 https://doi.org/10.1523/JNEUROSCI.0394-11.2011
Zic2 regulates the expression of Sert to modulate eye-specific refinement at the visual targets Garcia-Frigola C, Herrera E EMBO J 2010 29(18):3170 https://doi.org/10.1038/emboj.2010.172

Related News

A study co-led by the Institute for Neurosciences CSIC-UMH uncovers a key link in the genetic communication of craniofacial development

A study by the Institute for Neurosciences CSIC-UMH reveals new mechanisms essential for the visual circuit development

Related Articles

EphA4 mediates ephrinB1-dependent adhesion in retinal ganglion cells.

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Multiomic Analysis of Neurons with Divergent Projection Patterns Identifies Novel Regulators of Axon Pathfinding

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A Zic2-regulated switch in a noncanonical Wnt/betacatenin pathway is essential for the formation of bilateral circuits

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