miR-193b-365 microcluster downstream of Fezf2 coordinates neuron-subtype identity and dendritic morphology in cortical projection neurons

Summary: Different neuron types develop characteristic axonal and dendritic arborizations that determine their inputs, outputs, and functions. Expression of fate-determinant transcription factors is essential for specification of their distinct identities. However, the mechanisms downstream of fate-...

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Main Authors: Asha Iyer, Lee O. Vaasjo, Verl B. Siththanandan, Rajan K C, Abbigail Thurmon, Mauren Akumuo, Victoria Lu, Chelsea Nnebe, Ramesh Nair, Maria J. Galazo, Suzanne Tharin
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Language:English
Published: Elsevier 2024-12-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004224027275
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author Asha Iyer
Lee O. Vaasjo
Verl B. Siththanandan
Rajan K C
Abbigail Thurmon
Mauren Akumuo
Victoria Lu
Chelsea Nnebe
Ramesh Nair
Maria J. Galazo
Suzanne Tharin
author_facet Asha Iyer
Lee O. Vaasjo
Verl B. Siththanandan
Rajan K C
Abbigail Thurmon
Mauren Akumuo
Victoria Lu
Chelsea Nnebe
Ramesh Nair
Maria J. Galazo
Suzanne Tharin
author_sort Asha Iyer
collection DOAJ
description Summary: Different neuron types develop characteristic axonal and dendritic arborizations that determine their inputs, outputs, and functions. Expression of fate-determinant transcription factors is essential for specification of their distinct identities. However, the mechanisms downstream of fate-determinant factors coordinating different aspects of neuron identity are not understood. Specifically, how distinct projection neurons develop appropriate dendritic arbors that determine their inputs is unknown. Here, we investigate this question in corticospinal and callosal projection neurons. We identified a mechanism linking the corticospinal/corticofugal identity gene Fezf2 with the regulation of dendritic development. We show that miR-193b∼365 microRNA cluster is regulated by Fezf2 and enriched in corticospinal neurons. miR-193b∼365 represses mitogen-activated protein kinase 8 (MAPK8) to regulate corticospinal dendritic development. miR-193b∼365 overexpression in callosal neurons abnormally reduces MAPK8 signal and dendritic complexity. Our findings show that regulation of MAPK8 via miR-193b∼365 cluster regulates dendritic development, providing a mechanism that coordinates projection neuron identity, specified by Fezf2, and neuron-specific dendritic morphology.
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spelling doaj-art-363a84bd98a54db7a3e8db7ae82b4ca12024-12-22T05:29:32ZengElsevieriScience2589-00422024-12-012712111500miR-193b-365 microcluster downstream of Fezf2 coordinates neuron-subtype identity and dendritic morphology in cortical projection neuronsAsha Iyer0Lee O. Vaasjo1Verl B. Siththanandan2Rajan K C3Abbigail Thurmon4Mauren Akumuo5Victoria Lu6Chelsea Nnebe7Ramesh Nair8Maria J. Galazo9Suzanne Tharin10Department of Neurosurgery, Stanford University, Stanford, CA 94305, USANeuroscience program, Tulane Brain Institute, Tulane University, New Orleans, LA 70118 USADepartment of Neurosurgery, Stanford University, Stanford, CA 94305, USADepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118 USADepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118 USADepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118 USADepartment of Neurosurgery, Stanford University, Stanford, CA 94305, USADepartment of Neurosurgery, Stanford University, Stanford, CA 94305, USA; Neurosciences PhD program, Stanford University, Stanford, CA 94305, USAStanford Center for Genomics and Personalized Medicine, Stanford, CA 94305, USANeuroscience program, Tulane Brain Institute, Tulane University, New Orleans, LA 70118 USA; Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118 USA; Corresponding authorDepartment of Neurosurgery, Stanford University, Stanford, CA 94305, USA; Division of Neurosurgery, Palo Alto Veterans Affairs Health Care System, Palo Alto, CA 94304, USA; Neurosciences PhD program, Stanford University, Stanford, CA 94305, USASummary: Different neuron types develop characteristic axonal and dendritic arborizations that determine their inputs, outputs, and functions. Expression of fate-determinant transcription factors is essential for specification of their distinct identities. However, the mechanisms downstream of fate-determinant factors coordinating different aspects of neuron identity are not understood. Specifically, how distinct projection neurons develop appropriate dendritic arbors that determine their inputs is unknown. Here, we investigate this question in corticospinal and callosal projection neurons. We identified a mechanism linking the corticospinal/corticofugal identity gene Fezf2 with the regulation of dendritic development. We show that miR-193b∼365 microRNA cluster is regulated by Fezf2 and enriched in corticospinal neurons. miR-193b∼365 represses mitogen-activated protein kinase 8 (MAPK8) to regulate corticospinal dendritic development. miR-193b∼365 overexpression in callosal neurons abnormally reduces MAPK8 signal and dendritic complexity. Our findings show that regulation of MAPK8 via miR-193b∼365 cluster regulates dendritic development, providing a mechanism that coordinates projection neuron identity, specified by Fezf2, and neuron-specific dendritic morphology.http://www.sciencedirect.com/science/article/pii/S2589004224027275Biological sciencesEpigeneticsDevelopmental neuroscience
spellingShingle Asha Iyer
Lee O. Vaasjo
Verl B. Siththanandan
Rajan K C
Abbigail Thurmon
Mauren Akumuo
Victoria Lu
Chelsea Nnebe
Ramesh Nair
Maria J. Galazo
Suzanne Tharin
miR-193b-365 microcluster downstream of Fezf2 coordinates neuron-subtype identity and dendritic morphology in cortical projection neurons
iScience
Biological sciences
Epigenetics
Developmental neuroscience
title miR-193b-365 microcluster downstream of Fezf2 coordinates neuron-subtype identity and dendritic morphology in cortical projection neurons
title_full miR-193b-365 microcluster downstream of Fezf2 coordinates neuron-subtype identity and dendritic morphology in cortical projection neurons
title_fullStr miR-193b-365 microcluster downstream of Fezf2 coordinates neuron-subtype identity and dendritic morphology in cortical projection neurons
title_full_unstemmed miR-193b-365 microcluster downstream of Fezf2 coordinates neuron-subtype identity and dendritic morphology in cortical projection neurons
title_short miR-193b-365 microcluster downstream of Fezf2 coordinates neuron-subtype identity and dendritic morphology in cortical projection neurons
title_sort mir 193b 365 microcluster downstream of fezf2 coordinates neuron subtype identity and dendritic morphology in cortical projection neurons
topic Biological sciences
Epigenetics
Developmental neuroscience
url http://www.sciencedirect.com/science/article/pii/S2589004224027275
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