Latrophilin GPCR signaling mediates synapse formation DOI Creative Commons
Richard Sando, Thomas C. Südhof

eLife, Journal Year: 2021, Volume and Issue: 10

Published: March 1, 2021

Neural circuit assembly in the brain requires precise establishment of synaptic connections, but mechanisms synapse remain incompletely understood. Latrophilins are postsynaptic adhesion-GPCRs that engage trans-synaptic complexes with presynaptic teneurins and FLRTs. In mouse CA1-region neurons, Latrophilin-2 Latrophilin-3 essential for formation entorhinal-cortex-derived Schaffer-collateral-derived synapses, respectively. However, it is unknown whether latrophilins function as GPCRs formation. Here, we show exhibit constitutive GPCR activity increases cAMP levels, which was blocked by a mutation interfering G-protein arrestin interactions GPCRs. The same impaired ability to rescue synapse-loss phenotype knockout neurons vivo. Our results suggest require signaling formation, indicating promote hippocampus activating classical GPCR-signaling pathway.

Language: Английский

Perivascular neurons instruct 3D vascular lattice formation via neurovascular contact DOI

Kenichi Toma,

Mengya Zhao, Shaobo Zhang

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(11), P. 2767 - 2784.e23

Published: May 1, 2024

Language: Английский

Citations

12
Cadherin 4 assembles a family of color-preferring retinal circuits that respond to light offset DOI

Aline Giselle Rangel Olguin,

Pierre‐Luc Rochon,

Catherine Theriault

et al.

Current Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1
Positional Strategies for Connection Specificity and Synaptic Organization in Spinal Sensory-Motor Circuits DOI Creative Commons

Nikolaos Balaskas,

L. F. Abbott,

Thomas M. Jessell

et al.

Neuron, Journal Year: 2019, Volume and Issue: 102(6), P. 1143 - 1156.e4

Published: May 8, 2019

Language: Английский

Citations

67
Spatiotemporally Asymmetric Excitation Supports Mammalian Retinal Motion Sensitivity DOI Creative Commons
Akihiro Matsumoto, Kevin L. Briggman, Keisuke Yonehara

et al.

Current Biology, Journal Year: 2019, Volume and Issue: 29(19), P. 3277 - 3288.e5

Published: Sept. 26, 2019

Language: Английский

Citations

60
δ-Catenin controls astrocyte morphogenesis via layer-specific astrocyte–neuron cadherin interactions DOI Creative Commons
Christabel Xin Tan,

Dhanesh Sivadasan Bindu,

Evelyn J. Hardin

et al.

The Journal of Cell Biology, Journal Year: 2023, Volume and Issue: 222(11)

Published: Aug. 29, 2023

Astrocytes control the formation of specific synaptic circuits via cell adhesion and secreted molecules. Astrocyte synaptogenic functions are dependent on establishment their complex morphology. However, it is unknown if distinct neuronal cues differentially regulate astrocyte morphogenesis. δ-Catenin was previously thought to be a neuron-specific protein that regulates dendrite We found δ-catenin also highly expressed by astrocytes required both in neurons for hypothesized mediate transcellular interactions through cadherin family proteins. used structural modeling biochemical analyses reveal interacts with N-cadherin juxtamembrane domain promote surface expression. An autism-linked point mutation impaired expression reduced complexity. In developing mouse cortex, only lower-layer cortical express N-cadherin. Remarkably, when we silenced astrocytic throughout morphology disrupted. These findings show controls astrocyte-neuron layer-specific

Language: Английский

Citations

21
Brain wiring determinants uncovered by integrating connectomes and transcriptomes DOI Creative Commons
Juyoun Yoo, Mark Dombrovski,

Parmis Mirshahidi

et al.

Current Biology, Journal Year: 2023, Volume and Issue: 33(18), P. 3998 - 4005.e6

Published: Aug. 29, 2023

Advances in brain connectomics have demonstrated the extraordinary complexity of neural circuits.1,2,3,4,5 Developing neurons encounter axons and dendrites many different neuron types form synapses with only a subset them. During circuit assembly, express cell-type-specific repertoires comprising cell adhesion molecules (CAMs) that can mediate interactions between developing neurites.6,7,8 Many CAM families been shown to contribute wiring ways.9,10 It has challenging, however, identify receptor-ligand pairs directly matching their synaptic targets. Here, we integrated synapse-level connectome circuit11,12 developmental expression patterns7 binding specificities CAMs6,13 on pre- postsynaptic Drosophila visual system. To overcome circuits, focus genetically related make differential choices. In motion detection circuit,14 closely subtypes T4/T5 choose alternative targets adjacent layers neuropil.12 This choice correlates partners Beat Side CAMs. Genetic analysis presynaptic Side-II Beat-VI restrict same layer. Removal this pair disrupts leads inappropriate targeting sites dendrites. We propose Side/Beat collaborate other recognition determine fly brain. Combining transcriptomes, connectomes, protein interactome maps allow unbiased identification determinants wiring.

Language: Английский

Citations

19
Osteopontin drives retinal ganglion cell resiliency in glaucomatous optic neuropathy DOI Creative Commons
Mengya Zhao,

Kenichi Toma,

Benyam Kinde

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(9), P. 113038 - 113038

Published: Aug. 23, 2023

Chronic neurodegeneration and acute injuries lead to neuron losses via diverse processes. We compared retinal ganglion cell (RGC) responses between chronic glaucomatous conditions the injury model. Among major RGC subclasses, αRGCs intrinsically photosensitive RGCs (ipRGCs) preferentially survive conditions, similar findings in retina subject axotomy. Focusing on an αRGC intrinsic factor, Osteopontin (secreted phosphoprotein 1 [Spp1]), we found ectopic neuronal expression of (Spp1) other conditions. This contrasted with Spp1 downregulation αRGC-specific elimination led significant loss, diminishing their resiliency. overexpression robust neuroprotection susceptible subclasses under In contrast, did not significantly protect Additionally, SPP1 marked adult human subsets large somata aqueous humor correlated glaucoma severity. Our study reveals Spp1's role mediating resiliency glaucoma.

Language: Английский

Citations

18
Synaptic promiscuity in brain development DOI Creative Commons
Neele Wolterhoff, P. Robin Hiesinger

Current Biology, Journal Year: 2024, Volume and Issue: 34(3), P. R102 - R116

Published: Feb. 1, 2024

Precise synaptic connectivity is a prerequisite for the function of neural circuits, yet individual neurons, taken out their developmental context, readily form unspecific synapses. How does genome encode brain wiring in light this apparent contradiction? Synaptic specificity outcome long series processes and mechanisms before, during after synapse formation. much promiscuity permissible or necessary at moment partner choice depends on extent to which prior development restricts available partners subsequent corrects initially made can thereby play important roles precise connectivity, but also facilitate flexibility robustness. In review, we assess experimental evidence prevalence promiscuous formation development. Many well-established approaches are based genetic perturbation an assessment only adult; make it difficult pinpoint when given defect mechanism occurred. many cases, such studies reveal that restrict availability already Subsequently, choice, factors including competency, interaction dynamics molecular recognition further partners. The discussion through lens suggests algorithmic process neurons capable continuously prevented from making wrong choices, with no single time point sufficient explain outcome.

Language: Английский

Citations

8
Molecular mechanisms that mediate dendrite morphogenesis DOI
Julie L. Lefebvre

Current topics in developmental biology/Current Topics in Developmental Biology, Journal Year: 2021, Volume and Issue: unknown, P. 233 - 282

Published: Jan. 1, 2021

Language: Английский

Citations

37
To Stick or Not to Stick: The Multiple Roles of Cell Adhesion Molecules in Neural Circuit Assembly DOI Creative Commons
Trevor Moreland, Fabienne E. Poulain

Frontiers in Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: April 28, 2022

Precise wiring of neural circuits is essential for brain connectivity and function. During development, axons respond to diverse cues present in the extracellular matrix or at surface other cells navigate specific targets, where they establish precise connections with post-synaptic partners. Cell adhesion molecules (CAMs) represent a large group structurally proteins well known mediate circuit assembly. Through their adhesive properties, CAMs act as major regulators axon navigation, fasciculation, synapse formation. While functions have been decades, more recent studies unraveled essential, non-adhesive well. notably guidance modulate signaling pathways pathfinding, initiate contact-mediated repulsion spatial organization axonal arbors, refine neuronal projections during maturation. In this review, we summarize classical development further discuss increasing number play

Language: Английский

Citations

26