Emergence of planar cell polarity from the interplay of local interactions and global gradients DOI Creative Commons
Divyoj Singh, Sriraṁ Ramaswamy, Mohit Kumar Jolly

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: Dec. 1, 2021

Abstract Planar cell polarity (PCP) – tissue-scale alignment of the direction asymmetric localization proteins at cell-cell interface is essential for embryonic development and physiological functions. Abnormalities in PCP can lead to neural tube closure defects misaligned hair follicles. Decoding mechanism responsible establishment maintenance remains a fundamental open question. While roles various molecules broadly classified into “global” “local” modules have been well-studied, their necessity sufficiency explaining connecting perturbations experimentally observed patterns has not examined. Here, we develop minimal model that captures proposed features these global tissue-level gradient local distribution protein complexes. Our suggests while emerge without gradient, provide maintain robustly presence stochastic perturbations. We also recapitulated swirling seen domineering non-autonomy, using only three free parameters - binding rate, concentration forming heterodimer across boundaries steepness. explain how self-stabilizing localizations robust reveal design principles polarized system.

Language: Английский

The morphological and functional diversity of apical microvilli DOI Open Access
Maria Sharkova, Erica Chow, Timothy Erickson

et al.

Journal of Anatomy, Journal Year: 2022, Volume and Issue: 242(3), P. 327 - 353

Published: Oct. 25, 2022

Abstract Sensory neurons use specialized apical processes to perceive external stimuli and monitor internal body conditions. The apparatus can include cilia, microvilli, or both, is adapted for the functions of particular cell type. Photoreceptors detect light through a large, modified cilium (outer segment), that supported by surrounding ring microvilli‐like calyceal (CPs). Although first reported 150 years ago, CPs remain poorly understood. As basis future study, we therefore conducted review existing literature about sensory which act either as primary detector support cilia‐based detector. While all microvilli are finger‐like cellular protrusions with an actin core, vary across types in size, number, arrangement, dynamics, function. We summarize current state knowledge characteristics found on inner ear hair cells (stereocilia) cerebral spinal fluid‐contacting neurons, comparisons brush border intestinal renal epithelia. structure, stability, dynamics core regulated complement actin‐binding proteins, includes both common components unique features when compared types. Further, often lateral links, glycocalyx, defined extracellular matrix, each function environment cell. Our comparison microvillar will inform further research into how photoreceptor function, also provide general investigations structure neurons.

Language: Английский

Citations

24
Planar Cell Polarity Signaling: Coordinated Crosstalk for Cell Orientation DOI Creative Commons

Sandeep Kacker,

Varuneshwar Parsad,

Naveen Kumar Singh

et al.

Journal of Developmental Biology, Journal Year: 2024, Volume and Issue: 12(2), P. 12 - 12

Published: April 29, 2024

The planar cell polarity (PCP) system is essential for positioning cells in 3D networks to establish the proper morphogenesis, structure, and function of organs during embryonic development. PCP uses inter- intracellular feedback interactions between components core PCP, characterized by coordinated polarization asymmetric distribution populations inside cells. signaling connects anterior–posterior left–right plane through cilia Kupffer’s vesicle/node vertebrates. Experimental investigations on various genetic ablation-based models demonstrated functions associated disorders. This review paper aims provide a comprehensive overview history, pathway, molecular mechanisms underlying signaling, with other pathways, role organ Moreover, we will delve into negative regulation maintain polarity, human disorders defects, as well challenges PCP.

Language: Английский

Citations

4
Evolving Insights into Prickle2 in Neurodevelopment and Neurological Disorders DOI
Yi Yang,

Yanxia Mao,

Yao Zhang

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Language: Английский

Citations

0
Not a hair out of place: Polarizing and orienting sensory hair cells DOI
Katie S. Kindt, Basile Tarchini

Current topics in developmental biology/Current Topics in Developmental Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Regeneration of sensory hair cells in mature mammals DOI
Bradley J. Walters, Brandon C. Cox, Jennifer S. Stone

et al.

Current topics in developmental biology/Current Topics in Developmental Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
The dark kinase STK32A regulates hair cell planar polarity opposite of EMX2 in the developing mouse inner ear DOI Creative Commons
Shihai Jia,

Evan M. Ratzan,

Ellison J. Goodrich

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 5, 2023

The vestibular maculae of the inner ear contain sensory receptor hair cells that detect linear acceleration and contribute to equilibrioception coordinate posture ambulatory movements. These are divided between two groups, separated by a line polarity reversal (LPR), with oppositely oriented planar-polarized stereociliary bundles motion in opposite directions. transcription factor EMX2 is known establish this planar polarized organization mouse regulating distribution transmembrane GPR156 at cell boundaries one group cells. However, genes regulated context were previously not known. Using as model, we have identified serine threonine kinase STK32A downstream effector negatively EMX2. Stk32a expressed on side LPR pattern complementary Emx2 expression side. necessary align intrinsic bundle core (PCP) proteins EMX2-negative regions, sufficient reorient when ectopically neighboring EMX2-positive regions. We demonstrate reinforces formation apical localization GPR156. observations support model which orientation determined through separate mechanisms sides maculae, EMX2-mediated repression determining final position LPR.

Language: Английский

Citations

10
Junctional force patterning drives both positional order and planar polarity in the auditory epithelia DOI Creative Commons
Anubhav Prakash, Julian Weninger, Nishant Singh

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 25, 2025

Tissue function depends on the precise organisation of constituent cells. In cochlea, fidelity hearing mechanosensory hair cells being consistently surrounded by supporting addition to this positional order, auditory sensitivity crucially planar cell polarity. This is characterised alignment orientation eccentrically placed bundles each cell. These two levels order emerge simultaneously despite cellular fluxes that occur during cochlear development. However, link between tissue-scale rearrangements and intrinsic mechanisms remains unknown. By combining experimental theoretical approaches, we find a force patterning underpinning occurs through modulation phospho-type regulatory light chain non-muscle myosin II at specific cell-cell junctions epithelium. We propose control junctional mechanics vital for multi-cell-type epithelia.

Language: Английский

Citations

0
Gene therapy: an emerging therapy for hair cells regeneration in the cochlea DOI Creative Commons
Jipeng Wang, Jianwei Zheng, Haiyan Wang

et al.

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: May 3, 2023

Sensorineural hearing loss is typically caused by damage to the cochlear hair cells (HCs) due external stimuli or because of one’s genetic factors and inability convert sound mechanical energy into nerve impulses. Adult mammalian HCs cannot regenerate spontaneously; therefore, this type deafness usually considered irreversible. Studies on developmental mechanisms HC differentiation have revealed that nonsensory in cochlea acquire ability differentiate after overexpression specific genes, such as Atoh1 , which makes regeneration possible. Gene therapy, through vitro selection editing target transforms exogenous gene fragments alters expression genes activate corresponding program cells. This review summarizes been associated with growth development recent years provides an overview therapy approaches field regeneration. It concludes a discussion limitations current therapeutic facilitate early implementation clinical setting.

Language: Английский

Citations

9
Emx2 lineage tracing reveals antecedent patterns of planar polarity in the mouse inner ear DOI Creative Commons

Ellison J. Goodrich,

Michael R. Deans

Development, Journal Year: 2024, Volume and Issue: 151(10)

Published: April 29, 2024

The planar polarized organization of hair cells in the vestibular maculae is unique because these sensory organs contain two groups with oppositely oriented stereociliary bundles that meet at a line polarity reversal (LPR). EMX2 transcription factor expressed by one cell group reverses orientation their bundles, thereby forming LPR. We generated Emx2-CreERt2 transgenic mice for genetic lineage tracing and demonstrate Emx2 expression before specification when nascent utricle saccule constitute continuous prosensory domain. Precursors labeled this stage give rise to located along side LPR mature or saccule, indicating boundary first established Consistent this, Dreher mutants, where fail segregate, labels field fused utriculo-saccular-cochlear organ. These observations reveal positioning pre-determined developing domain, defines lineages bundles.

Language: Английский

Citations

2
RGS12 polarizes the GPSM2-GNAI complex to organize and elongate stereocilia in sensory hair cells DOI Creative Commons
Anıl Aktürk, Matthew Day, Basile Tarchini

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(42)

Published: Oct. 19, 2022

Inhibitory G proteins (GNAI/Gα

Language: Английский

Citations

11