A cochlear progenitor pool influences patterning of the mammalian sensory epithelium via MYBL2 DOI Creative Commons
Caryl A. Young, Emily K. Burt, Vidhya Munnamalai

et al.

Development, Journal Year: 2024, Volume and Issue: 151(17)

Published: Sept. 1, 2024

ABSTRACT During embryonic development, Wnt signaling influences both proliferation and sensory formation in the cochlea. How this dual nature of is coordinated unknown. In study, we define a novel role for Wnt-regulated gene, Mybl2, which was already known to be important proliferation, determining size patterning epithelium murine Using quantitative spatial analysis approach analyzing Mybl2 loss-of-function, show that promoted inner sulcus domain but limited by influencing their adjoining boundary position via Jag1 regulation during development. loss-of-function simultaneously decreased increased domain, resulting wider with ectopic hair cell late stages. These data suggest progenitor cells determine pattern MYBL2.

Language: Английский

TMTC4 is a hair cell–specific human deafness gene DOI Creative Commons
Li Jiang, Byung Yoon Choi, Yasmin Eltawil

et al.

JCI Insight, Journal Year: 2023, Volume and Issue: 8(24)

Published: Nov. 14, 2023

Transmembrane and tetratricopeptide repeat 4 (Tmtc4) is a deafness gene in mice. Tmtc4-KO mice have rapidly progressive postnatal hearing loss due to overactivation of the unfolded protein response (UPR); however, cellular basis human relevance Tmtc4-associated cochlea was not heretofore appreciated. We created hair cell-specific conditional KO mouse that phenocopies constitutive with onset deafness, demonstrating Tmtc4 gene. Furthermore, we identified family which variants segregate adult-onset loss. Lymphoblastoid cells derived from multiple affected unaffected members, as well embryonic kidney engineered harbor each variants, demonstrated confer hypersensitivity UPR toward apoptosis. These findings provide evidence TMTC4 humans further implicate

Language: Английский

Citations

3
Inhibition of the long non‐coding RNA UNC5B‐AS1/miR‐4455/RSPO4 axis reduces cervical cancer growth in vitro and in vivo DOI
Jian Fu, Yuanyuan Zhang, Min Wang

et al.

The Journal of Gene Medicine, Journal Year: 2021, Volume and Issue: 23(12)

Published: Aug. 5, 2021

Long non-coding RNAs (lncRNAs) are significant regulatory factors for the initiation and development of numerous malignant tumors, including cervical cancer (CC). The expression lncRNA unc-5 netrin receptor B antisense RNA 1 (UNC5B-AS1, also known as UASR1) is up-regulated in tissues squamous cell carcinoma endocervical adenocarcinoma compared to normal based on GEPIA database. In present study, we explored functions UNC5B-AS1 its underlying mechanism with respect CC development.A real-time quantitative polymerase chain reaction was applied detection cells. Cell counting kit-8, colony formation transwell assays, well western blot flow cytometry analyses, were employed detect biological effects knockdown phenotypes cells vitro. addition, combination between microRNA-4455 (miR-4455) or R-spondin 4 (RSPO4) by immunoprecipitation, luciferase reporter pulldown assays. A tumor xenograft nude mice model established explore effect depletion miR-4455 overexpression growth.UNC5B-AS1 inhibits proliferation, migration invasion promotes apoptosis. Mechanistically, binds up-regulate RSPO4 expression. targeted negatively regulated vivo assays revealed that growth regulating expression.Inhibition UNC5B-AS1/miR-4455/RSPO4 reduces both vitro vivo, furnishing new insights into molecular studies development.

Language: Английский

Citations

7
Opposing effects of Wnt/β-catenin signaling on epithelial and mesenchymal cell fate in the developing cochlea DOI Creative Commons
Sara Billings,

Nina M. Myers,

Lee A. Quiruz

et al.

Development, Journal Year: 2021, Volume and Issue: 148(11)

Published: June 1, 2021

During embryonic development, the otic epithelium and surrounding periotic mesenchymal cells originate from distinct lineages coordinate to form mammalian cochlea. Epithelial sensory precursors within cochlear duct first undergo terminal mitosis before differentiating into non-sensory cells. In parallel, differentiate shape lateral wall, modiolus pericochlear spaces. Previously, Wnt activation was shown promote proliferation differentiation of both epithelial Here, we fate-mapped Wnt-responsive in mice found that resulted opposing cell fates. post-mitotic epithelium, via β-catenin stabilization induced clusters proliferative dedifferentiated lost characteristics. contrast, Wnt-activated mesenchyme formed ectopic spaces showing a loss gain features. Finally, clonal analyses multi-colored fate-mapping showed proliferated colonies, whereas assembled as aggregates mitotically quiescent Together, show drives transition between states type-dependent manner.

Language: Английский

Citations

6
Spatial and temporal expression of PORCN is highly dynamic in the developing mouse cochlea DOI

Brianna L. Oliver,

Caryl A. Young, Vidhya Munnamalai

et al.

Gene Expression Patterns, Journal Year: 2021, Volume and Issue: 42, P. 119214 - 119214

Published: Sept. 20, 2021

Language: Английский

Citations

6
A cochlear progenitor pool influences patterning of the mammalian sensory epithelium via MYBL2 DOI Creative Commons
Caryl A. Young, Emily K. Burt, Vidhya Munnamalai

et al.

Development, Journal Year: 2024, Volume and Issue: 151(17)

Published: Sept. 1, 2024

ABSTRACT During embryonic development, Wnt signaling influences both proliferation and sensory formation in the cochlea. How this dual nature of is coordinated unknown. In study, we define a novel role for Wnt-regulated gene, Mybl2, which was already known to be important proliferation, determining size patterning epithelium murine Using quantitative spatial analysis approach analyzing Mybl2 loss-of-function, show that promoted inner sulcus domain but limited by influencing their adjoining boundary position via Jag1 regulation during development. loss-of-function simultaneously decreased increased domain, resulting wider with ectopic hair cell late stages. These data suggest progenitor cells determine pattern MYBL2.

Language: Английский

Citations

0