Postnatal Dynamic Ciliary ARL13B and ADCY3 Localization in the Mouse Brain DOI Creative Commons

Katlyn K. Brewer,

Kathryn M. Brewer, Tiffany T. Terry

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 259 - 259

Published: Jan. 30, 2024

Primary cilia are hair-like structures found on nearly all mammalian cell types, including cells in the developing and adult brain. A diverse set of receptors signaling proteins localize within to regulate many physiological developmental pathways, Hedgehog (Hh) pathway. Defects structure, protein localization, function lead genetic disorders called ciliopathies, which present with various clinical features that include several neurodevelopmental phenotypes hyperphagia-associated obesity. Despite their dysfunction being implicated disease states, understanding roles central nervous system (CNS) development has proven challenging. We hypothesize dynamic changes ciliary composition contribute this challenge may reflect unrecognized diversity CNS cilia. The ARL13B ADCY3 established markers is a regulatory GTPase important for regulating trafficking, Hh signaling, adenylyl cyclase. Here, we examine localization perinatal mouse define proportion enriched depending brain region age. Furthermore, identify distinct lengths specific regions male female mice. ARL13B+ become relatively rare age regions, hypothalamic feeding centers, while becomes prominent marker mature It understand endogenous patterns these throughout under different conditions as common be more than initially expected. Understanding regional- developmental-associated signatures condition reveal molecular mechanisms associated commonly observed ciliopathy models like obesity diabetes.

Language: Английский

Primary cilia as dynamic and diverse signalling hubs in development and disease DOI
Pleasantine Mill, Søren T. Christensen, Lotte B. Pedersen

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(7), P. 421 - 441

Published: April 18, 2023

Language: Английский

Citations

178
Volume electron microscopy DOI
Christopher J. Peddie, Christel Genoud, Anna Kreshuk

et al.

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: July 7, 2022

Language: Английский

Citations

123
Rhythmic cilia changes support SCN neuron coherence in circadian clock DOI

Hai-Qing Tu,

Sen Li,

Yu-Ling Xu

et al.

Science, Journal Year: 2023, Volume and Issue: 380(6648), P. 972 - 979

Published: June 1, 2023

The suprachiasmatic nucleus (SCN) drives circadian clock coherence through intercellular coupling, which is resistant to environmental perturbations. We report that primary cilia are required for coupling among SCN neurons maintain the robustness of internal in mice. Cilia neuromedin S-producing (NMS) exhibit pronounced rhythmicity abundance and length. Genetic ablation ciliogenesis NMS enabled a rapid phase shift under jet-lag conditions. rhythms individual cilia-deficient slices lost their after external Rhythmic changes drive oscillations Sonic Hedgehog (Shh) signaling gene expression. Inactivation Shh phenocopied effects ablation. Thus, cilia-Shh aids coupling.

Language: Английский

Citations

46
Emerging mechanistic understanding of cilia function in cellular signalling DOI
Keren I. Hilgendorf, Benjamin R. Myers, Jeremy F. Reiter

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(7), P. 555 - 573

Published: Feb. 16, 2024

Language: Английский

Citations

43
Mitochondrial dysfunction compromises ciliary homeostasis in astrocytes DOI Creative Commons
Olesia Ignatenko, Satu Malinen,

Sofiia Rybas

et al.

The Journal of Cell Biology, Journal Year: 2022, Volume and Issue: 222(1)

Published: Nov. 16, 2022

Astrocytes, often considered as secondary responders to neurodegeneration, are emerging primary drivers of brain disease. Here we show that mitochondrial DNA depletion in astrocytes affects their cilium, the signaling organelle a cell. The progressive oxidative phosphorylation deficiency induces FOXJ1 and RFX transcription factors, known master regulators motile ciliogenesis. Consequently, robust gene expression program involving cilia components multiciliated cell differentiation factors induced. While affected still retain single these organelles elongate become remarkably distorted. data suggest chronic activation integrated stress response (ISRmt) drives anabolic metabolism promotes ciliary elongation. Collectively, our evidence indicates an active axis mitochondria exists is part ISRmt astrocytes. We propose metabolic ciliopathy novel pathomechanism for mitochondria-related neurodegenerative diseases.

Language: Английский

Citations

50
Organizing principles of astrocytic nanoarchitecture in the mouse cerebral cortex DOI Creative Commons
Christopher Salmon, Tabish A. Syed,

J. Benjamin Kacerovsky

et al.

Current Biology, Journal Year: 2023, Volume and Issue: 33(5), P. 957 - 972.e5

Published: Feb. 16, 2023

Language: Английский

Citations

35
Mapping of neuronal and glial primary cilia contactome and connectome in the human cerebral cortex DOI Creative Commons

Jun Yao Wu,

S. J. Cho,

Katherine D. Descant

et al.

Neuron, Journal Year: 2023, Volume and Issue: 112(1), P. 41 - 55.e3

Published: Oct. 28, 2023

Language: Английский

Citations

34
Primary cilia TRP channel regulates hippocampal excitability DOI Creative Commons

Thuy N. Vien,

My C. Ta,

Louise F. Kimura

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(22)

Published: May 22, 2023

Polycystins (PKD2, PKD2L1, and PKD2L2) are members of the transient receptor potential family, which form ciliary ion channels. Most notably, PKD2 dysregulation in kidney nephron cilia is associated with polycystic disease, but function PKD2L1 neurons undefined. In this report, we develop animal models to track expression subcellular localization brain. We discover that localizes functions as a Ca 2+ channel primary hippocampal apically radiate from soma. Loss ablates maturation attenuates neuronal high-frequency excitability, precipitates seizure susceptibility autism spectrum disorder–like behavior mice. The disproportionate impairment interneuron excitability suggests circuit disinhibition underlies neurophenotypic features these Our results identify channels regulators organelle mediators brain electrical signaling.

Language: Английский

Citations

23
GPR161 structure uncovers the redundant role of sterol-regulated ciliary cAMP signaling in the Hedgehog pathway DOI

Nicholas Hoppe,

Simone Harrison, Sun‐Hee Hwang

et al.

Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: 31(4), P. 667 - 677

Published: Feb. 7, 2024

Language: Английский

Citations

13
Light-microscopy based dense connectomic reconstruction of mammalian brain tissue DOI Creative Commons
Mojtaba R. Tavakoli,

Julia Lyudchik,

Michał Januszewski

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 2, 2024

Abstract The information-processing capability of the brain’s cellular network depends on physical wiring pattern between neurons and their molecular functional characteristics. Mapping resolving individual synaptic connections can be achieved by volumetric imaging at nanoscale resolution with dense labeling. Light microscopy is uniquely positioned to visualize specific molecules but dense, synapse-level circuit reconstruction light has been out reach due limitations in resolution, contrast, capability. Here we developed light-microscopy based connectomics (LICONN). We integrated specifically engineered hydrogel embedding expansion comprehensive deep-learning segmentation analysis connectivity, thus directly incorporating information brain tissue reconstructions. LICONN will allow phenotyping biological experiments a readily adoptable manner. One-Sentence Summary Hydrogel enables molecularly informed microscopy.

Language: Английский

Citations

12