Lagging Brain Gene Expression Patterns of Drosophila melanogaster Young Adult Males Confound Comparisons Between Sexes DOI Creative Commons
Flannery McLamb, Zuying Feng, Jeanne P. Vu

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 28, 2024

Abstract Many species, including fruit flies ( Drosophila melanogaster ), are sexually dimorphic. Phenotypic variation in morphology, physiology, and behavior can affect development, reproduction, health, aging. Therefore, designating sex as a variable sex-blocking should be considered when designing experiments. The brain regulates phenotypes throughout the lifespan by balancing survival sex-specific development at each life stage is likely. Changes morphology physiology governed differential gene expression, quantifiable molecular marker for age- variations. We assessed fly transcriptome three adult ages expression signatures of sex, age, sex-by-age: 6698 genes were differentially expressed between sexes, with most divergence 3 days. Between ages, 31.1% 6084 (1890 genes) share similar patterns from to 7 days females, 14 males. Most these (90.5%, 1712) upregulated enriched chemical stimulus detection and/or cilium regulation. Our data highlight an important delay male regulation compared females. Because significant delays could confound comparisons studies sexual dimorphism phenotypically comparable stages rather than chronological age more biologically relevant.

Language: Английский

Motile cilia modulate neuronal and astroglial activity in the zebrafish larval brain DOI Creative Commons
Percival P. D’Gama, Inyoung Jeong, Andreas Moe Nygård

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(1), P. 115195 - 115195

Published: Jan. 1, 2025

Language: Английский

Citations

2
The neuronal cilium – a highly diverse and dynamic organelle involved in sensory detection and neuromodulation DOI Creative Commons
Nathalie Jurisch‐Yaksi, Dagmar Wachten, Jay Gopalakrishnan

et al.

Trends in Neurosciences, Journal Year: 2024, Volume and Issue: 47(5), P. 383 - 394

Published: April 4, 2024

Cilia are fascinating organelles that act as cellular antennae, sensing the environment. gained significant attention in late 1990s after their dysfunction was linked to genetic diseases known ciliopathies. Since then, several breakthrough discoveries have uncovered mechanisms underlying cilia biogenesis and function. Like most cells animal kingdom, neurons also harbor cilia, which enriched neuromodulatory receptors. Yet, how neuronal modulate physiology behavior remains poorly understood. By comparing ciliary biology between sensory central nervous systems (CNS), we provide new perspectives on functions of brain physiology.

Language: Английский

Citations

12
LRRC56 deletion causes primary ciliary dyskinesia in mice characterized by dynein arms defects DOI Creative Commons

Ruolan Wu,

Huilong Li,

Pingyun Wu

et al.

Biology Open, Journal Year: 2025, Volume and Issue: 14(2)

Published: Feb. 5, 2025

ABSTRACT Leucine Rich Repeat Containing protein 56 (LRRC56), also known as DNAAF12, is a member of the LRRC superfamily, whose dysfunction associated with mucociliary clearance and laterality defects in humans. Here, we generated LRRC56-knockout mice using CRISPR/Cas9 nuclease system to specifically target exons 4-5 LRRC56 gene. We observed that homozygous gene deletion definitely deleterious, 27.8% LRRC56−/− died before adulthood. Among surviving mice, most prominent phenotypes included hydrocephalus, situs inversus, male infertility, bronchiectasis. Transmission electron microscopy revealed dynein arms cilia disorganized axonemal structure flagella. Immunofluorescence analysis similarly absence inner outer arm markers DNALI1 DNAI2 cilia. Heterozygous LRRC56+/− developed normally, without exhibiting any symptoms primary ciliary dyskinesia. In conclusion, knockout leads range conditions consistent The signaling mouse supports critical role assembly.

Language: Английский

Citations

1
Ciliogenesis defects after neurulation impact brain development and neuronal activity in larval zebrafish DOI Creative Commons

Percival P D'Gama,

Inyoung Jeong, Andreas Moe Nygård

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 110078 - 110078

Published: May 22, 2024

Language: Английский

Citations

4
Multicilia dynamically transduce Shh signaling to regulate choroid plexus functions DOI Open Access

Suifang Mao,

Rui Song, Shibo Jin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Choroid plexus is a major site for cerebrospinal fluid (CSF) production, characterized by multiciliated epithelial monolayer that regulates CSF production. We demonstrate defective choroid ciliogenesis or Intraflagellar transport yields neonatal hydrocephalus, at least in part, due to increased water channel Aqp1 and ion transporter Atp1a2 expression. multicilia as sensory cilia, transducing both canonical non-canonical Shh signaling. Interestingly, it the signaling represses expression Smo/Gαi/cAMP pathway. exhibit unique ciliary ultrastructure, carrying features of primary motile cilia. Unlike most cilia elongate during maturation, length decreases development, causing decline intensity developing plexus, derepression Atp1a2, ultimately, an Hence, developmental dynamics dampens promote

Language: Английский

Citations

0
Multicilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions DOI Creative Commons

Suifang Mao,

Rui Song, Shibo Jin

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(3), P. 115383 - 115383

Published: March 1, 2025

Highlights•Choroid plexus cilia defects contribute to a neonatal hydrocephalus phenotype•Choroid exhibit distinct ultrastructure resembling primary and motile cilia•Choroid transduce Shh repress water channel ion transporter expression•Developmental dynamics of choroid ciliary length governs the signaling intensitySummaryThe is major site for cerebrospinal fluid (CSF) production, characterized by multiciliated epithelial monolayer that regulates CSF production. We demonstrate defective ciliogenesis or intraflagellar transport yields hydrocephalus, at least in part due increased Aqp1 Atp1a2 expression. multicilia as sensory cilia, transducing both canonical non-canonical Sonic Hedgehog (Shh) signaling. Interestingly, it represses expression Smoothened (Smo)/Gαi/cyclic AMP (cAMP) pathway. Choroid unique ultrastructure, carrying features cilia. Unlike most elongate during maturation, decreases development, causing decline intensity developing plexus, derepression Atp1a2, and, ultimately, Hence, developmental dampens promote production.Graphical abstract

Language: Английский

Citations

0
Cilia-mediated cerebrospinal fluid flow modulates neuronal and astroglial activity in the zebrafish larval brain. DOI Creative Commons
Percival P. D’Gama, Inyoung Jeong, Andreas Moe Nygård

et al.

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

Published: Feb. 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.

Language: Английский

Citations

2
Single cell transcriptional analysis of human adenoids identifies molecular features of airway microfold cells DOI Creative Commons
Samuel Álvarez-Arguedas, Khadijah Mazhar, Andi Wangzhou

et al.

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

Published: Oct. 22, 2024

Abstract The nasal, oropharyngeal, and bronchial mucosa are primary contact points for airborne pathogens like Mycobacterium tuberculosis (Mtb), SARS-CoV-2, influenza virus. While mucosal surfaces can function as both entry barriers to infection, mucosa-associated lymphoid tissues (MALT) facilitate early immune responses antigens. MALT contains a variety of specialized epithelial cells, including rare cell type called microfold (M cell) that functions transport apical antigens basolateral antigen-presenting crucial step in the initiation immunity. M cells have been extensively characterized gastrointestinal (GI) tract murine human models. However, precise development airway is unknown. Here, using single-nucleus RNA sequencing (snRNA-seq), we generated an atlas from adenoid identified 16 unique types representing basal, club, hillock, hematopoietic lineages, defined their developmental trajectories, determined cell-cell relationships. Using trajectory analysis, found develop progenitor club express gene signature distinct intestinal cells. Surprisingly, also heretofore unknown demonstrating robust interferon-stimulated signature. Our analysis enhances our understanding role This work provides resource interactions with platform vaccines.

Language: Английский

Citations

1
Rbm24 maintains survival of cochlear outer hair cells by repressing Insm1 DOI Creative Commons
Chao Li,

Luyue Wang,

Shuting Li

et al.

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

Published: June 29, 2024

ABSTRACT The inactivation of Rbm24, an RNA-binding protein, results in the degeneration cochlear outer hair cells (OHCs) during postnatal period. However, specific molecular mechanisms underlying this OHC death remain elusive. To address this, we conducted a comprehensive analysis comparing gene profiles wild-type OHCs to those lacking Rbm24 ( -/- ) at day 7 (P7). Our revealed that overall differentiation program is delayed absence Rbm24. Furthermore, expression Insm1, crucial factor for development normally switched off by P2, remains prolonged OHCs. Interestingly, when Insm1 overexpressed, it also leads death. Significantly, much less severe both and are simultaneously inactivated. These findings shed light on important role repressing its impact survival. study provides valuable insights into complex genetic signaling pathways involved development.

Language: Английский

Citations

0
Increased SNAI2 expression and defective collagen adhesion in cells with pediatric dementia, juvenile ceroid lipofuscinosis DOI
Hyungkuen Kim,

Sung Jin Bae,

Sung‐Jo Kim

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 738, P. 150561 - 150561

Published: Aug. 15, 2024

Language: Английский

Citations

0