Reelin and cofilin cooperate during the migration of cortical neurons: A quantitative morphological analysis

Chai, Xuejun; Zhao, Shanting; Fan, Li; Zhang, Wei; Lu, Xi; Shao, Haibao; Wang, Shaobo; Song, Lingzhen; Failla, Antonio Virgilio; Zobiak, Bernd; Mannherz, Hans Georg; Frotscher, Michael

doi:10.1242/dev.134163

Cited by 37 publications

(39 citation statements)

References 117 publications

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“…Chai et al (2009) then demonstrated that the amounts of phosphorylated cofilin are significantly reduced in reeler and that application of recombinant Reelin to reeler tissue significantly increased the phosphorylation of cofilin, suggesting that Reelin-induced cofilin phosporylation is important for the normal lamination of the cerebral cortex. This hypothesis was recently confirmed by in utero electroporation (IUE) experiments (Chai et al, 2016). Transfection of newly born cortical neurons with a non-phosphorylatable form of cofilin ( cofilin S3A ) revealed a significant migration defect of the transfected cells, which remained near their site of origin in the subventricular zone (SVZ)—very much reminiscent of the reeler phenotype.…”

Section: Reelin Acts Upstream Of Cofilin To Facilitate Migrationmentioning

confidence: 75%

“…Sections were counterstained with propidium iodide (PI). Scale bar: 100 μm (from Chai et al, 2016, reproduced with permission).…”

Section: Reelin Acts Upstream Of Cofilin To Facilitate Migrationmentioning

confidence: 99%

“…Neurons in reeler slices transfected with LIMK1 or cofilin S3E show a normal leading process oriented toward the MZ. Scale bar: 15 μm (from Chai et al, 2016, reproduced with permission).…”

Section: Reelin Acts On Both Neurons and Radial Glial Cellsmentioning

confidence: 99%

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Reelin Signaling Inactivates Cofilin to Stabilize the Cytoskeleton of Migrating Cortical Neurons

Frotscher

Zhao

Wang

et al. 2017

Front. Cell. Neurosci.

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Neurons are highly polarized cells. They give rise to several dendrites but only one axon. In addition, many neurons show a preferred orientation. For example, pyramidal neurons of the cerebral cortex extend their apical dendrites toward the cortical surface while their axons run in opposite direction toward the white matter. This characteristic orientation reflects the migratory trajectory of a pyramidal cell during cortical development: the leading process (the future apical dendrite) extends toward the marginal zone (MZ) and the trailing process (the future axon) toward the intermediate zone (IZ) while the cells migrate radially to reach their destination in the cortical plate (CP). In this review article, we summarize the function of Reelin, an extracellular matrix protein synthesized by Cajal-Retzius cells in the MZ, in the development of the characteristic orientation of the leading processes running perpendicular to the cortical surface. Reelin promotes migration toward the cortical surface since late-generated cortical neurons in the reeler mutant are unable to reach upper cortical layers. Likewise, Reelin is important for the orientation and maintenance of the leading processes of migrating neurons since they are misoriented in the developing reeler cortex, as are the apical dendrites of pyramidal cells in the mature mutant. Reelin-induced phosphorylation of cofilin, an actin-associated protein, is crucial since pyramidal neurons transfected by in utero electroporation (IUE) with a non-phosphorylatable form of cofilin (cofilinS3A) show severe migration defects reminiscent of those in the reeler mutant. Remarkably, migration of neurons in the cortex of reeler mice was partially rescued by transfecting them with LIM kinase 1 (LIMK1), the kinase that induces phosphorylation of cofilin at serine3, or with a pseudo-phosphorylated cofilin mutant (cofilinS3E). Together these results indicate that Reelin-induced phosphorylation of cofilin is an important component in the orientation and directed migration of cortical neurons and in their correct lamination.

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Section: Reelin Acts Upstream Of Cofilin To Facilitate Migrationmentioning

confidence: 75%

“…Sections were counterstained with propidium iodide (PI). Scale bar: 100 μm (from Chai et al, 2016, reproduced with permission).…”

Section: Reelin Acts Upstream Of Cofilin To Facilitate Migrationmentioning

confidence: 99%

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Reelin Signaling Inactivates Cofilin to Stabilize the Cytoskeleton of Migrating Cortical Neurons

Frotscher

Zhao

Wang

et al. 2017

Front. Cell. Neurosci.

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“…F. Bradke (DZNE, Bonn) kindly provided the Lifeact‐GFP plasmid. M. Kneussel (ZMNH, UKE) kindly provided the EB3‐GFP and X. Chai (from the laboratory of M. Frotscher, ZMNH, UKE) kindly gave us the Cofilin‐GFP and Cofilin‐S3E‐GFP constructs . Cofilin‐S3E‐RFP was a gift from James Bamburg (Addgene plasmid # 50858; http://n2t.net/addgene:50858; ).…”

Section: Methodsmentioning

confidence: 99%

Radial somatic F‐actin organization affects growth cone dynamics during early neuronal development

et al. 2019

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The centrosome is thought to be the major neuronal microtubule‐organizing center (MTOC) in early neuronal development, producing microtubules with a radial organization. In addition, albeit in vitro, recent work showed that isolated centrosomes could serve as an actin‐organizing center, raising the possibility that neuronal development may, in addition, require a centrosome‐based actin radial organization. Here, we report, using super‐resolution microscopy and live‐cell imaging of cultured rodent neurons, F‐actin organization around the centrosome with dynamic F‐actin aster‐like structures with F‐actin fibers extending and retracting actively. Photoactivation/photoconversion experiments and molecular manipulations of F‐actin stability reveal a robust flux of somatic F‐actin toward the cell periphery. Finally, we show that somatic F‐actin intermingles with centrosomal PCM‐1 (pericentriolar material 1 protein) satellites. Knockdown of PCM‐1 and disruption of centrosomal activity not only affect F‐actin dynamics near the centrosome but also in distal growth cones. Collectively, the data show a radial F‐actin organization during early neuronal development, which might be a cellular mechanism for providing peripheral regions with a fast and continuous source of actin polymers, hence sustaining initial neuronal development.

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“…As mentioned above, Reelin signaling activates LIMK1, which results in enhanced n-cofilin activation (Chai et al, 2009). A recent study showed that migration defect in the IZ of reeler mice was partially rescued by overexpression of LIMK1 or a phosphomimic mutant of cofilin (Chai et al, 2016). These findings suggest that Reelin signaling influences neuronal migration in the IZ.…”

Section: Roles Of Reelin Signaling In the Radial Migration Of Neuronsmentioning

confidence: 99%

Control of Neuronal Migration and Aggregation by Reelin Signaling in the Developing Cerebral Cortex

Hirota

Nakajima

2017

Front. Cell Dev. Biol.

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The mammalian cerebral neocortex has a well-organized laminar structure, achieved by the highly coordinated control of neuronal migration. During cortical development, excitatory neurons born near the lateral ventricle migrate radially to reach their final positions to form the cortical plate. During this process, dynamic changes are observed in the morphologies and migration modes, including multipolar migration, locomotion, and terminal translocation, of the newborn neurons. Disruption of these migration processes can result in neuronal disorders such as lissencephaly and periventricular heterotopia. The extracellular protein, Reelin, mainly secreted by the Cajal-Retzius neurons in the marginal zone during development, plays a crucial role in the neuronal migration and neocortical lamination. Reelin signaling, which exerts essential roles in the formation of the layered neocortex, is triggered by the binding of Reelin to its receptors, ApoER2 and VLDLR, followed by phosphorylation of the Dab1 adaptor protein. Accumulating evidence suggests that Reelin signaling controls multiple steps of neuronal migration, including the transition from multipolar to bipolar neurons, terminal translocation, and termination of migration beneath the marginal zone. In addition, it has been shown that ectopically expressed Reelin can cause neuronal aggregation via an N-cadherin-mediated manner. This review attempts to summarize our knowledge of the roles played by Reelin in neuronal migration and the underlying mechanisms.

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Reelin and cofilin cooperate during the migration of cortical neurons: A quantitative morphological analysis

Cited by 37 publications

References 117 publications

Reelin Signaling Inactivates Cofilin to Stabilize the Cytoskeleton of Migrating Cortical Neurons

Reelin Signaling Inactivates Cofilin to Stabilize the Cytoskeleton of Migrating Cortical Neurons

Radial somatic F‐actin organization affects growth cone dynamics during early neuronal development

Control of Neuronal Migration and Aggregation by Reelin Signaling in the Developing Cerebral Cortex

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