CLASP2 Links Reelin to the Cytoskeleton during Neocortical Development

Dillon, Gregory M.; Tyler, William A.; Omuro, Kerilyn C.; Kambouris, John; Tyminski, Camila; Henry, Shawna; Haydar, Tarik F.; Beffert, Uwe; Ho, Angela

doi:10.1016/j.neuron.2017.02.039

Cited by 34 publications

(40 citation statements)

References 63 publications

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“…The inhibition of CLASP2 decreases axon and dendritic length without affecting the morphology of the Golgi. CLASP2 mRNA level is upregulated in adult reeler mice and its knockdown inhibits neurite growth induced by Reelin on cultured neurons [ 197 ]. CLASP2 interacts with Dab1 but the phosphorylation state of Dab1 does not control CLASP2 binding, and it is not known whether Reelin influences this interaction.…”

Section: Reelin Signaling and Dendritic Growthmentioning

confidence: 99%

Reelin Functions, Mechanisms of Action and Signaling Pathways During Brain Development and Maturation

2020

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During embryonic development and adulthood, Reelin exerts several important functions in the brain including the regulation of neuronal migration, dendritic growth and branching, dendritic spine formation, synaptogenesis and synaptic plasticity. As a consequence, the Reelin signaling pathway has been associated with several human brain disorders such as lissencephaly, autism, schizophrenia, bipolar disorder, depression, mental retardation, Alzheimer’s disease and epilepsy. Several elements of the signaling pathway are known. Core components, such as the Reelin receptors very low-density lipoprotein receptor (VLDLR) and Apolipoprotein E receptor 2 (ApoER2), Src family kinases Src and Fyn, and the intracellular adaptor Disabled-1 (Dab1), are common to most but not all Reelin functions. Other downstream effectors are, on the other hand, more specific to defined tasks. Reelin is a large extracellular protein, and some aspects of the signal are regulated by its processing into smaller fragments. Rather than being inhibitory, the processing at two major sites seems to be fulfilling important physiological functions. In this review, I describe the various cellular events regulated by Reelin and attempt to explain the current knowledge on the mechanisms of action. After discussing the shared and distinct elements of the Reelin signaling pathway involved in neuronal migration, dendritic growth, spine development and synaptic plasticity, I briefly outline the data revealing the importance of Reelin in human brain disorders.

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Section: Reelin Signaling and Dendritic Growthmentioning

confidence: 99%

Reelin Functions, Mechanisms of Action and Signaling Pathways During Brain Development and Maturation

2020

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“…This stimulated motility occurred via ApoeR2, activating Cdc42 through the PI3K cascade, which resulted in axonal filopodia formation [169]. More recently, Clasp2 (cytoplasmic linker associated proteins), an MT plus-end tracking protein that specifically accumulates in the growth cone, was also shown to be a key cytoskeletal effector downstream of the Reln activation pathway, orchestrating cytoskeletal dynamics during neurite extension and motility during brain development [170].…”

Section: 214b Animal Models and Functional Studiesmentioning

confidence: 99%

Genetics and mechanisms leading to human cortical malformations

Romero

Bahi‐Buisson

Francis

2018

Seminars in Cell & Developmental Biology

101

109

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“…Interaction between the SFK Fyn and serine/threonine kinase family member Cdk5 are evidenced to play a leading role in progenitor cell axon guidance and dendritic orientation (Sasaki et al, 2002 ; Figure 4 ). Reelin and Dab1 alter cytoskeleton morphology through CLASP2 (Dillon et al, 2017 ). Cux1 and Cux2 regulate dendritic morphology through Pax6 and p27 in pyramidal neurons (Nieto et al, 2004 ).…”

Section: Cortical Developmentmentioning

confidence: 99%

Estradiol and the Development of the Cerebral Cortex: An Unexpected Role?

Denley¹,

Gatford²,

Sellers³

et al. 2018

Front. Neurosci.

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The cerebral cortex undergoes rapid folding in an “inside-outside” manner during embryonic development resulting in the establishment of six discrete cortical layers. This unique cytoarchitecture occurs via the coordinated processes of neurogenesis and cell migration. In addition, these processes are fine-tuned by a number of extracellular cues, which exert their effects by regulating intracellular signaling pathways. Interestingly, multiple brain regions have been shown to develop in a sexually dimorphic manner. In many cases, estrogens have been demonstrated to play an integral role in mediating these sexual dimorphisms in both males and females. Indeed, 17β-estradiol, the main biologically active estrogen, plays a critical organizational role during early brain development and has been shown to be pivotal in the sexually dimorphic development and regulation of the neural circuitry underlying sex-typical and socio-aggressive behaviors in males and females. However, whether and how estrogens, and 17β-estradiol in particular, regulate the development of the cerebral cortex is less well understood. In this review, we outline the evidence that estrogens are not only present but are engaged and regulate molecular machinery required for the fine-tuning of processes central to the cortex. We discuss how estrogens are thought to regulate the function of key molecular players and signaling pathways involved in corticogenesis, and where possible, highlight if these processes are sexually dimorphic. Collectively, we hope this review highlights the need to consider how estrogens may influence the development of brain regions directly involved in the sex-typical and socio-aggressive behaviors as well as development of sexually dimorphic regions such as the cerebral cortex.

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CLASP2 Links Reelin to the Cytoskeleton during Neocortical Development

Cited by 34 publications

References 63 publications

Reelin Functions, Mechanisms of Action and Signaling Pathways During Brain Development and Maturation

Reelin Functions, Mechanisms of Action and Signaling Pathways During Brain Development and Maturation

Genetics and mechanisms leading to human cortical malformations

Estradiol and the Development of the Cerebral Cortex: An Unexpected Role?

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