foxg1a is required for hair cell development and regeneration in the zebrafish lateral line

Biology Open, Год журнала: 2024, Номер 13(9)

Опубликована: Сен. 15, 2024

ABSTRACT Mechanosensory hair cells located in the inner ear mediate sensations of hearing and balance. If damaged, mammalian are unable to regenerate, resulting permanent sensory deficits. Aquatic vertebrates like zebrafish (Danio rerio) have a specialized class mechanosensory found lateral line system, allowing them sense changes water current. Unlike cells, can robustly regenerate following damage. In mammals, transcription factor Foxg1 functions promote normal development ear. Foxg1a is expressed organs larvae, but its function during regeneration has not been investigated. Our study demonstrates that mutation foxg1a results slower posterior primordium migration delayed neuromast formation. developing regenerating neuromasts, we find loss reduced cell numbers, as well decreased proliferation cells. specifically regulates Islet1-labeled These data suggest may be valuable target for investigation clinical regeneration.

Язык: Английский

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Zebrahub-Multiome: Uncovering Gene Regulatory Network Dynamics During Zebrafish Embryogenesis

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

Опубликована: Окт. 19, 2024

During embryonic development, gene regulatory networks (GRNs) drive molecular differentiation of cell types. However, the temporal dynamics these remain poorly understood. Here, we present Zebrahub-Multiome, a comprehensive, time-resolved atlas zebrafish embryogenesis, integrating single-cell chromatin accessibility (scATAC-seq) and expression (scRNA-seq) from over 94,000 cells sampled across six key developmental stages (10 to 24 hours post-fertilization). Our analysis reveals early-stage GRNs shared multiple lineages, followed by emergence lineage-specific programs during later stages. We also observe shift in transcription factor (TF) influence broad, multi-lineage roles early development more specialized, cell-type-specific functions as progresses. Using silico genetic perturbations, highlight dynamic role TFs driving fate decisions, emphasizing gradual specialization circuits. All data analyses are made accessible through an interactive web portal, enabling users explore time This resource provides foundation for hypothesis generation deeper insights into vertebrate development.

Язык: Английский

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Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes

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

Опубликована: Окт. 22, 2024

Regeneration and homeostatic turnover of solid tissues depend on the proliferation symmetrically dividing adult stem cells, which either remain cells or differentiate based their niche position. Here we demonstrate that in zebrafish lateral line sensory organs, progenitor cell are independently regulated by two

Язык: Английский

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Long-range Atoh1 enhancers maintain competency for hair cell regeneration in the inner ear

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(51)

Опубликована: Дек. 13, 2024

During tissue regeneration, lineage-related cells can switch their fate to replace missing cells. This cell plasticity is particularly prominent in more regenerative vertebrates such as zebrafish, yet the molecular basis by which transdifferentiate into another type upon injury remains unclear. Here, we investigate epigenetic of transdifferentiation inner ear, where supporting (SCs) generate mechanosensory hair (HCs) damage. By comparing chromatin landscapes zebrafish and green anole lizards versus nonregenerative mice, identified a class enhancers that function progenitors HCs then are selectively maintained SCs regenerate HCs. In particular, uncovered syntenic long-range for Atoh1 , master transcription factor HC differentiation. absence injury, these maintain accessibility through adulthood but prevented from driving atoh1a expression Notch repression. Deletion not only impaired formation during development also blocked ability regeneration. Moreover, defects were specific ear lateral line, revealing distinct mechanisms regeneration organs. These findings reveal enhancer maintains competency upregulate We propose continued developmental one may be common theme underlying adult vertebrates.

Язык: Английский

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Off the deep end: What can deep learning do for the gene expression field?

Journal of Biological Chemistry, Год журнала: 2022, Номер 299(1), С. 102760 - 102760

Опубликована: Ноя. 30, 2022

After a COVID-related hiatus, the fifth biennial symposium on Evolution and Core Processes in Gene Regulation met at Stowers Institute Kansas City, Missouri July 21 to 24, 2022. This symposium, sponsored by American Society for Biochemistry Molecular Biology (ASBMB), featured experts gene regulation evolutionary biology. Topic areas covered enhancer evolution, cis-regulatory code, regulatory variation, with an overall focus bringing power of deep learning (DL) decipher DNA sequence information. DL is machine method that uses neural networks learn complex rules make predictions about diverse types data. When models are trained predict genomic data from information, their high prediction accuracy allows identification impactful genetic variants within across species. In addition, learned can be extracted model provide important clues mechanistic underpinnings code.

Язык: Английский

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