JNK Signaling Regulates Cellular Mechanics of Cortical Interneuron Migration

Smith, Skye E.; Coker, Nicholas K.; Tucker, Eric S.

doi:10.1523/eneuro.0132-20.2020

Cited by 5 publications

(4 citation statements)

References 61 publications

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“…However, in Actin-Cre ERT2 (Cre +/− ), Mkk4 ∆/∆ , Mkk7 ∆/∆ mice, these cells were disarranged, since they were displaced over the GCL, maintaining immature cell markers. These finding suggest that MKK4 and MKK7 have a role in adult neuroblast migration and differentiation processes, in accordance with the results obtained by Smith, Coker, and Tucker, who identified that the JNK signaling pathway is a regulator of branching and nucleokinesis during the migration of cortical interneurons [33]. In this respect, Nestin-Cre, Mkk7 flox/flox mice showed severe defects along embryonic brain development in radial migration and axonal growth [8].…”

Section: The Deletion Of Mkk4 and Mkk7 Gene Alters Immature Hippocampal Neuronssupporting

confidence: 88%

Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells

Castro-Torres

Olloquequi

Etchetto

et al. 2021

IJMS

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(1) Background: The c-Jun-NH2-terminal protein kinase (JNK) is a mitogen-activated protein kinase involved in regulating physiological processes in the central nervous system. However, the dual genetic deletion of Mkk4 and Mkk7 (upstream activators of JNK) in adult mice is not reported. The aim of this study was to induce the genetic deletion of Mkk4/Mkk7 in adult mice and analyze their effect in hippocampal neurogenesis. (2) Methods: To achieve this goal, Actin-CreERT2 (Cre+/−), Mkk4flox/flox, Mkk7flox/flox mice were created. The administration of tamoxifen in these 2-month-old mice induced the gene deletion (Actin-CreERT2 (Cre+/−), Mkk4∆/∆, Mkk7∆/∆ genotype), which was verified by PCR, Western blot, and immunohistochemistry techniques. (3) Results: The levels of MKK4/MKK7 at 7 and 14 days after tamoxifen administration were not eliminated totally in CNS, unlike what happens in the liver and heart. These data could be correlated with the high levels of these proteins in CNS. In the hippocampus, the deletion of Mkk4/Mkk7 induced a misalignment position of immature hippocampal neurons together with alterations in their dendritic architecture pattern and maturation process jointly to the diminution of JNK phosphorylation. (4) Conclusion: All these data supported that the MKK4/MKK7–JNK pathway has a role in adult neurogenic activity.

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Section: The Deletion Of Mkk4 and Mkk7 Gene Alters Immature Hippocampal Neuronssupporting

confidence: 88%

Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells

Castro-Torres

Olloquequi

Etchetto

et al. 2021

IJMS

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“…The role of JNK in axon guidance within the Dlx5/6 territory has not yet been explored; however, our lab recently identified a novel role for JNK signaling in the migration of cortical interneurons arising from the Dlx5/6 lineage. [26][27][28] Since the Dlx5/6 territory instructs thalamocortical axon pathfinding and disruptions to JNK signaling alter axonal development, we sought to determine whether JNK signaling was required within Dlx5/6 cells to establish major longitudinal axon pathways in the forebrain.…”

Section: Introductionmentioning

confidence: 99%

Early construction of the thalamocortical axon pathway requires c‐Jun N‐terminal kinase signaling within the ventral forebrain

Cunningham

Scripter

Nti

et al. 2021

Developmental Dynamics

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Background: Thalamocortical connectivity is essential for normal brain function. This important pathway is established during development, when thalamic axons extend a long distance through the forebrain before reaching the cerebral cortex. In this study, we identify a novel role for the c-Jun N-terminal kinase (JNK) signaling pathway in guiding thalamocortical axons through intermediate target territories. Results: Complete genetic removal of JNK signaling from the Distal-less 5/6 (Dlx5/6) domain in mice prevents thalamocortical axons from crossing the diencephalon-telencephalon boundary (DTB) and the internal capsule fails to form. Ventral telencephalic cells critical for thalamocortical axon extensions including corridor and guidepost neurons are also disrupted. In addition, corticothalamic, striatonigral, and nigrostriatal axons fail to cross the DTB. Analyses of different JNK mutants demonstrate that thalamocortical axon pathfinding has a non-autonomous requirement for JNK signaling. Conclusions:We conclude that JNK signaling within the Dlx5/6 territory enables the construction of major axonal pathways in the developing forebrain. Further exploration of this intermediate axon guidance territory is needed to uncover mechanisms of axonal pathfinding during normal brain development and to elucidate how this vital process may be compromised in neurodevelopmental disorders.

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“…This occurs due to an early switch from tangential to radial migration and premature entry in the cortical plate ( Myers et al, 2020 ). Further, the loss of Jnk in cINs leads to alterations of leading process branching dynamics through reduced growth cone splitting and shortening of the swelling extension in the leading process, together with an aberrant localization of the centrosome and primary cilium to the trailing process ( Smith et al, 2020b ). Overall, JNK plays critical roles in regulating cIN migration, downstream of Rac1/Pak1.…”

Section: Cell-intrinsic Regulation Of Cin Migration Dynamicsmentioning

confidence: 99%

Interneuron odyssey: molecular mechanisms of tangential migration

Toudji,

Toumi,

Chamberland

et al. 2023

Front. Neural Circuits

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Cortical GABAergic interneurons are critical components of neural networks. They provide local and long-range inhibition and help coordinate network activities involved in various brain functions, including signal processing, learning, memory and adaptative responses. Disruption of cortical GABAergic interneuron migration thus induces profound deficits in neural network organization and function, and results in a variety of neurodevelopmental and neuropsychiatric disorders including epilepsy, intellectual disability, autism spectrum disorders and schizophrenia. It is thus of paramount importance to elucidate the specific mechanisms that govern the migration of interneurons to clarify some of the underlying disease mechanisms. GABAergic interneurons destined to populate the cortex arise from multipotent ventral progenitor cells located in the ganglionic eminences and pre-optic area. Post-mitotic interneurons exit their place of origin in the ventral forebrain and migrate dorsally using defined migratory streams to reach the cortical plate, which they enter through radial migration before dispersing to settle in their final laminar allocation. While migrating, cortical interneurons constantly change their morphology through the dynamic remodeling of actomyosin and microtubule cytoskeleton as they detect and integrate extracellular guidance cues generated by neuronal and non-neuronal sources distributed along their migratory routes. These processes ensure proper distribution of GABAergic interneurons across cortical areas and lamina, supporting the development of adequate network connectivity and brain function. This short review summarizes current knowledge on the cellular and molecular mechanisms controlling cortical GABAergic interneuron migration, with a focus on tangential migration, and addresses potential avenues for cell-based interneuron progenitor transplants in the treatment of neurodevelopmental disorders and epilepsy.

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JNK Signaling Regulates Cellular Mechanics of Cortical Interneuron Migration

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Cited by 5 publications

References 61 publications

Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells

Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells

Early construction of the thalamocortical axon pathway requires c‐Jun N‐terminal kinase signaling within the ventral forebrain

Interneuron odyssey: molecular mechanisms of tangential migration

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