Optogenetic control of the Dab1 signaling pathway

Wang, Liang; Cooper, Jonathan A.

doi:10.1038/srep43760

Cited by 5 publications

(4 citation statements)

References 47 publications

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“…The clustering of Dab1 through VLDLR and ApoER2 therefore triggers a positive activation loop and a localized amplification of tyrosine kinase activity. Dab1 dimerization is sufficient on its own to induce phosphorylation [ 130 , 144 ]. Mice carrying mutations in Dab1 on the five important tyrosine residues, organotypic brain slices inhibited for SFK kinase activity using a specific small molecule inhibitor, and double knockout mice for Src and Fyn exhibit a reeler-like phenotype [ 142 , 145 , 146 , 147 ].…”

Section: Reelin Signaling and Neuronal Migrationmentioning

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 Neuronal Migrationmentioning

confidence: 99%

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

2020

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“…This property of oligomerization was later improved with a small change in sequences (93, 94). As many signaling events are initiated by homo-oligomerization, particularly receptor signaling, they have been widely applied to many signaling pathways (95–100).…”

Section: Experimental Strategies For Engineering or Modulating Dynamimentioning

confidence: 99%

Techniques for Studying Decoding of Single Cell Dynamics

2019

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Cells must be able to interpret signals they encounter and reliably generate an appropriate response. It has long been known that the dynamics of transcription factor and kinase activation can play a crucial role in selecting an individual cell's response. The study of cellular dynamics has expanded dramatically in the last few years, with dynamics being discovered in novel pathways, new insights being revealed about the importance of dynamics, and technological improvements increasing the throughput and capabilities of single cell measurements. In this review, we highlight the important developments in this field, with a focus on the methods used to make new discoveries. We also include a discussion on improvements in methods for engineering and measuring single cell dynamics and responses. Finally, we will briefly highlight some of the many challenges and avenues of research that are still open.

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“…Using this method one can investigate how changes in individual cells influence neighboring cells and global tissue remodeling. So far, most experiments applying optogenetics for studying cell-migration have mainly been applied to in vitro cell culture systems and small in vivo systems, e.g., during gastrulation ( Wang et al, 2010 ; Kim et al, 2014 ; Weitzman and Hahn, 2014 ; Valon et al, 2017 ; Wang and Cooper, 2017 ). In the mouse brain, optogenetics have mainly been used to activate, inhibit, or detect neuronal activity ( Montagni et al, 2019 ).…”

Section: Cellular Assays To Analyze and Genetically Dissect Non-cell-mentioning

confidence: 99%

Non-Cell-Autonomous Mechanisms in Radial Projection Neuron Migration in the Developing Cerebral Cortex

Hansen

Hippenmeyer

2020

Front. Cell Dev. Biol.

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Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final target lamina, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating the specific sequential steps of radial neuronal migration in vivo are however still unclear, let alone the effects and interactions with the extracellular environment. In any in vivo context, cells will always be exposed to a complex extracellular environment consisting of (1) secreted factors acting as potential signaling cues, (2) the extracellular matrix, and (3) other cells providing cell-cell interaction through receptors and/or direct physical stimuli. Most studies so far have described and focused mainly on intrinsic cell-autonomous gene functions in neuronal migration but there is accumulating evidence that noncell-autonomous-, local-, systemic-, and/or whole tissue-wide effects substantially contribute to the regulation of radial neuronal migration. These non-cell-autonomous effects may differentially affect cortical neuron migration in distinct cellular environments. However, the cellular and molecular natures of such non-cell-autonomous mechanisms are mostly unknown. Furthermore, physical forces due to collective migration and/or community effects (i.e., interactions with surrounding cells) may play important roles in neocortical projection neuron migration. In this concise review, we first outline distinct models of non-cell-autonomous interactions of cortical projection neurons along their radial migration trajectory during development. We then summarize experimental assays and platforms that can be utilized to visualize and potentially probe non-cell-autonomous mechanisms. Lastly, we define key questions to address in the future.

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Optogenetic control of the Dab1 signaling pathway

Cited by 5 publications

References 47 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

Techniques for Studying Decoding of Single Cell Dynamics

Non-Cell-Autonomous Mechanisms in Radial Projection Neuron Migration in the Developing Cerebral Cortex

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