δ-Catenin controls astrocyte morphogenesis via layer-specific astrocyte–neuron cadherin interactions

Tan, Christabel Xin; Bindu, Dhanesh Sivadasan; Hardin, Evelyn J.; Sakers, Kristina; Baumert, Ryan; Ramirez, Juan J.; Savage, Justin T.; Eroglu, Cagla

doi:10.1083/jcb.202303138

Cited by 17 publications

(7 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tight junctions are not necessary in this context, because there is no need to delineate internal and external surfaces within an inner neuropil. Interestingly, recent work on astrocyte-neuron interactions in visual cortex revealed that cadherin-catenin adhesion complexes between neurons and astrocytes regulate astrocyte morphogenesis, suggesting that modified adherens junctions may also be present at sites of neuron-glia contact in the mammalian brain (Tan et al, 2023). Thus, neurons and glia – which are developmentally derived from epithelia – may form attachments to one another by repurposing epithelial adherens junction machinery.…”

Section: Discussionmentioning

confidence: 99%

SAX-7/L1CAM acts with the adherens junction proteins MAGI-1, HMR-1/Cadherin, and AFD-1/Afadin to promote glial-mediated dendrite extension

Cebul,

Marivin,

Wexler

et al. 2024

Preprint

View full text Add to dashboard Cite

Adherens junctions (AJs) are a fundamental organizing structure for multicellular life. Although AJs are studied mainly in epithelia, their core function - stabilizing cell contacts by coupling adhesion molecules to the cytoskeleton - is important in diverse tissues. We find that two C. elegans sensory neurons, URX and BAG, require conserved AJ proteins for dendrite morphogenesis. We previously showed that URX and BAG dendrites attach to the embryonic nose via the adhesion molecule SAX-7/L1CAM, acting both in neurons and glia, and then extend by stretch during embryo elongation. Here, we find that a PDZ-binding motif (PB) in the SAX-7 cytoplasmic tail acts with other interaction motifs to promote dendrite extension. Using pull-down assays, we find that the SAX-7 PB binds the multi-PDZ scaffolding protein MAGI-1, which bridges it to the cadherin-catenin complex protein HMP-2/β-catenin. Using cell-specific rescue and depletion, we find that both MAGI-1 and HMR-1/Cadherin act in glia to non-autonomously promote dendrite extension. Double mutant analysis indicates that each protein can act independently of SAX-7, suggesting a multivalent adhesion complex. The SAX-7 PB motif also binds AFD-1/Afadin, loss of which further enhances sax-7 BAG dendrite defects. As MAGI-1, HMR-1, and AFD-1 are all found in epithelial AJs, we propose that an AJ-like complex in glia promotes dendrite extension.

show abstract

Section: Discussionmentioning

confidence: 99%

SAX-7/L1CAM acts with the adherens junction proteins MAGI-1, HMR-1/Cadherin, and AFD-1/Afadin to promote glial-mediated dendrite extension

Cebul,

Marivin,

Wexler

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Synapse quantification was performed as previously described [54,64,110]. Briefly, synapse analysis was performed using immunohistochemistry on three independent brain sections per group.…”

Section: Methodsmentioning

confidence: 99%

Astrocytic thrombospondins 1 and 2 are required for cortical synapse development controlling instrumental performance

Lawal,

Ulloa Severino,

Wang

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

During development, controlled synaptogenesis is required to form functioning neural circuits that underlie cognition and behavior. Astrocytes, a major glial-cell type in the central nervous system (CNS), promote synapse formation by secreting synaptogenic proteins. Thrombospondins 1 and 2 (TSP1/2), which act through their neuronal receptor α2δ-1, are required for proper intracortical excitatory synaptogenesis. In the adult brain, the loss of α2δ-1 impairs training-induced excitatory synaptogenesis in the anterior cingulate cortex (ACC), and this impairment leads to increased effort-exertion during high-effort tasks. Here, we tested whether TSP1 and TSP2 are required for controlling effort during operant conditioning by using a lever press for food reward training in mice. Surprisingly, we found that constitutive loss of TSP1/2 significantly reduced lever pressing performance when the effort required for a food reward was increased, a phenotype opposite of α2δ-1 loss. Loss of TSP1/2 reduced excitatory synapse number significantly in adult brains. However, in the ACC of TSP1/2 knockout mice, there was still training-induced excitatory synaptogenesis, likely through the upregulation of TSP4, a TSP isoform that is also synaptogenic. Unexpectedly, we also found a significant increase in inhibitory synapse number and function in the ACC of TSP1/2 knockout mice, which was eliminated after training. Finally, we found that astrocyte-specific ablation of TSP1/2 in developing but not adult astrocytes is sufficient to reduce performance during high-effort tasks. Taken together, our study highlights the importance of developmental astrocyte-derived synaptogenic cues TSP1 and 2 in establishing excitatory and inhibitory circuits that control effort during operant conditioning in adults.

show abstract

“…Brain cells communicate through tree-shaped extensions that process and transmit information 1 . These miniaturized arbors mediate all cognition and behavior 2,a , and their branching is altered in most neurological and psychiatric conditions 3 , from Alzheimer's disease 4,5 to autism spectrum disorders [6][7][8] . Scientists use microscopes to trace these structures into computer files allowing investigation of neural function, but the process is slow and costly 9,10 .…”

Section: Introductionmentioning

confidence: 99%

Accelerating the continuous community sharing of digital neuromorphology data

Tecuatl,

Ljungquist,

Ascoli

2024

Preprint

View full text Add to dashboard Cite

The tree-like morphology of neurons and glia is a key cellular determinant of circuit connectivity and metabolic function in the nervous system of essentially all animals. To elucidate the contribution of specific cell types to both physiological and pathological brain states, it is important to access detailed neuroanatomy data for quantitative analysis and computational modeling. NeuroMorpho.Org is the largest online collection of freely available digital neural reconstructions and related metadata and is continuously updated with new uploads. Earlier in the project, we released multiple datasets together yearly, but this process caused an average delay of several months in making the data public. Moreover, in the past 5 years, >80% of invited authors agreed to share their data with the community via NeuroMorpho.Org, up from <20% in the first 5 years of the project. In the same period, the average number of reconstructions per publication increased 600%, creating the need for automatic processing to release more reconstructions in less time. The progressive automation of our pipeline enabled the transition to agile releases of individual datasets as soon as they are ready. The overall time from data identification to public sharing decreased by 63.7%; 78% of the datasets are now released in less than 3 months with an average workflow duration below 40 days. Furthermore, the mean processing time per reconstruction dropped from 3 hours to 2 minutes. With these continuous improvements, NeuroMorpho.Org strives to forge a positive culture of open data. Most importantly, the new, original research enabled through reuse of datasets across the world has a multiplicative effect on science discovery, benefiting both authors and users.

show abstract

δ-Catenin controls astrocyte morphogenesis via layer-specific astrocyte–neuron cadherin interactions

Cited by 17 publications

References 84 publications

SAX-7/L1CAM acts with the adherens junction proteins MAGI-1, HMR-1/Cadherin, and AFD-1/Afadin to promote glial-mediated dendrite extension

SAX-7/L1CAM acts with the adherens junction proteins MAGI-1, HMR-1/Cadherin, and AFD-1/Afadin to promote glial-mediated dendrite extension

Astrocytic thrombospondins 1 and 2 are required for cortical synapse development controlling instrumental performance

Accelerating the continuous community sharing of digital neuromorphology data

Contact Info

Product

Resources

About