Advances in Imaging Techniques for Mammalian/Human Ciliated Cell’s Cilia: Insights into Structure, Function, and Dynamics

Biology, Год журнала: 2025, Номер 14(5), С. 521 - 521

Опубликована: Май 8, 2025

Cilia are evolutionarily conserved, microtubule-based organelles characterized by their ultrastructures and diverse functional roles, including developmental signaling, mechanosensation, fluid propulsion. They widely distributed across cell surfaces play crucial roles in cycle regulation tissue homeostasis. Despite advances studying molecular functions, demonstrating the precise ultrastructure of cilia remains a challenge. Recent novel microscopy techniques, such as super-resolution volume electron microscopy, revolutionizing our understanding architecture mechanochemical signaling. By integrating findings from different methodologies, this review highlights how these bridge basic research clinical applications provide comprehensive structural organization, mechanisms, dynamic changes cilia.

Язык: Английский

---

Cilia-mediated cerebrospinal fluid flow modulates neuronal and astroglial activity in the zebrafish larval brain.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 2, 2024

The brain uses a specialized system to transport cerebrospinal fluid (CSF). This consists of interconnected ventricles lined by ependymal cells, which generate directional flow upon beating their motile cilia. Motile cilia act jointly with other physiological factors, including active CSF secretion and cardiac pressure gradients, regulate dynamics. content movement are thought be important for physiology. Yet, the link between cilia-mediated function is poorly understood. In this study, we addressed role on development physiology using zebrafish larvae as model system. By analyzing mutant animals paralyzed cilia, identified that loss ciliary motility did not alter progenitor proliferation, overall morphology, or spontaneous neural activity. Instead, paralysis led randomization asymmetry. We also observed altered neuronal responses photic stimulation, especially in optic tectum hindbrain. Since astroglia contact at ventricular walls essential regulating activity, next investigated astroglial activity mutants. Our analyses revealed striking reduction calcium signals both during light-evoked Altogether, our findings highlight novel through modulation networks.

Язык: Английский

---

Multiciliogenesis: Tricking the cell-cycle machinery to build hundreds of cilia

Current Biology, Год журнала: 2024, Номер 34(16), С. R786 - R788

Опубликована: Авг. 1, 2024

Язык: Английский

---

Myocardin-Related Transcription Factor Mediates Epithelial Fibrogenesis in Polycystic Kidney Disease

Cells, Год журнала: 2024, Номер 13(11), С. 984 - 984

Опубликована: Июнь 5, 2024

Polycystic kidney disease (PKD) is characterized by extensive cyst formation and progressive fibrosis. However, the molecular mechanisms whereby loss/loss-of-function of Polycystin 1 or 2 (PC1/2) provokes fibrosis are largely unknown. The small GTPase RhoA has been recently implicated in

Язык: Английский

---

Direct quantitative perturbations of physical parameters in vivo to elucidate vertebrate embryo morphogenesis

Current Opinion in Cell Biology, Год журнала: 2024, Номер 90, С. 102420 - 102420

Опубликована: Авг. 24, 2024

Physical parameters such as tissue interplay forces, luminal pressure, fluid flow, temperature, and electric fields are crucial regulators of embryonic morphogenesis. While significant attention has been given to cellular molecular responses these physical parameters, their roles in morphogenesis not yet fully elucidated. This is largely due a shortage methods for spatiotemporal modulation direct quantitative perturbation embryos. Recent advancements addressing challenges include microscopes equipped with devices apply adjust the application micro-forces targeted cells cilia vivo. These critical unveiling mechanisms, highlighting importance integrating approaches comprehensive understanding

Язык: Английский

---

Primary cilia in Parkinson’s disease: summative roles in signaling pathways, genes, defective mitochondrial function, and substantia nigra dopaminergic neurons

Frontiers in Aging Neuroscience, Год журнала: 2024, Номер 16

Опубликована: Сен. 18, 2024

Primary cilia (PC) are microtubules-based, independent antennal-like sensory organelles, that seen in most vertebrate cells of different types, including astrocytes and neurons. They send signals to control many physiological cellular processes by detecting changes the extracellular environment. Parkinson’s disease (PD), a neurodegenerative progresses over time, is primarily caused gradual degradation dopaminergic pathway striatum nigra, which results large loss neurons substantia nigra compact (SNpc) depletion dopamine (DA). PD samples have abnormalities structure function PC. The alterations contribute cause, development, recovery via influencing signaling pathways (SHH, Wnt, Notch-1, α-syn, TGFβ), genes (MYH10 LRRK2), defective mitochondrial function, Thus, restoring normal PC brain effective treatment for PD. This review summarizes diseases explores pathological mechanisms PD, order provide references ideas future research.

Язык: Английский

---

Regulation of the Cilia as a Potential Treatment for Senescence and Tumors: A Review

Journal of Cellular Physiology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 11, 2024

Millions of people worldwide die from malignant tumors every year, and the current clinical treatment is still based on radiotherapy chemotherapy. Immunotherapy-adjuvant chemotherapy widely applied, yet resistance to various factors persists in management advanced malignancies. Recently researchers have gradually discovered that integrity primary cilia closely related many diseases. The phenotypic changes are found some cases progeria, tumorigenesis, drug resistance. Primary seem mediate signaling during these Hedgehog inhibitors emerged recent years treat by controlling proteins cilia. There evidence for use anti-tumor drugs senescence-related disease. Considering close relationship between aging obesity, as well obesity phenotype ciliopathies. Therefore, we speculate or anti-aging can Additionally, there suggesting tumor treatment, which process may be mediated This review elucidates first time involved regulation senescence, metabolic, hypothesizes regulated diseases future.

Язык: Английский

---

BBSome-dependent ciliary Hedgehog signaling governs cell fate in the white adipose tissue

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 25, 2024

The primary cilium has emerged as critical in regulating whole-body energy metabolism, reflected the Bardet-Biedl syndrome (BBS) where cilia dysfunction leads to obesity due hyperphagia and white adipose tissue (WAT) remodeling. regulation of cell fate differentiation adipocyte precursor cells (APCs) is key maintaining WAT homeostasis during obesity. Using mice that recapitulated BBS patient phenotype (Bbs8-/-), we demonstrate reduces stem-cell-like P1 APC subpopulation by inducing a phenotypic switch into fibrogenic progenitor state, characterized extracellular matrix (ECM) remodeling upregulation CD9. Single-cell RNA sequencing revealed direct transition progenitors, bypassing committed P2 cells. Ectopic ciliary Hedgehog signaling upon loss BBS8 central driver molecular changes Bbs8-/- APCs, altering adipocytes lipid uptake. These findings unravel novel role for governing fate, determining delicate balance between adipogenesis fibrogenesis. identified mechanisms provide insights potential therapeutic targets

Язык: Английский

---

Loss of Bbs8 leads to cystic kidney disease in mice and affects tubulin acetylation through HDAC2

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 12, 2024

Abstract Bardet-Biedl Syndrome (BBS) is a genetic disorder marked by considerable and phenotypic diversity. BBS often presents as combination of retinitis pigmentosa, obesity, polydactyly, cystic kidney disease considered model ciliopathy. The syndrome caused pathogenic variants in genes, some which encode components ciliary multi-protein complex, known the BBSome, well chaperonin-like required for BBSome assembly. In this study, we describe occurrence cysts mouse model. Specifically, loss BBS8 led to development end first year life. addition transcriptional changes key genes involved regulated cell death inflammation, proteomic approaches revealed increased expression altered phosphorylation histone deacetylase HDAC2 knockout kidneys. Consistently, Bbs8 resulted reduction acetylated alpha-tubulin primary cilia. This leads diminished stability dynamics cilia, potentially contributing formation kidneys other manifestations previously described deficient mice.

Язык: Английский

---

Myocardin-related transcription factor drives epithelial fibrogenesis in polycystic kidney disease

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 17, 2024

Abstract Polycystic kidney disease (PKD) is characterized by extensive cyst formation and progressive fibrosis. However, the molecular mechanisms whereby loss/loss-of-function of Polycystin 1 or 2 (PC1/2) provokes fibrosis are largely unknown. The small GTPase RhoA has been recently implicated in cystogenesis , we have shown that RhoA/cytoskeleton/myocardin-related transcription factor (MRTF) pathway a key mediator epithelium-induced fibrogenesis. Therefore, hypothesized MRTF activated PC1/2 loss plays critical role fibrogenic reprogramming epithelium. Loss PC1 PC2 induced siRNA vitro RhoA, caused cytoskeletal remodeling robust nuclear translocation overexpression. These phenomena were also manifest PKD1 (RC/RC) PKD2 (WS25/-) mice, with overexpression occurring predominantly dilated tubules cyst-lining epithelium, respectively. In epithelial cells, large cohort PC1/PC2 downregulation-induced genes was MRTF-dependent, including cytoskeletal, integrin-related, matricellular/fibrogenic proteins. Epithelial necessary for paracrine priming fibroblast-myofibroblast transition. Thus, novel loss-induced profibrotic phenotype, consequently PKD-related

Язык: Английский

---