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Cited by 161RNA Research and SplicingCancer-related molecular mechanisms researchDevelopmental Biology and Gene Regulation

The splicing regulators Esrp1 and Esrp2 direct an epithelial splicing program essential for mammalian development

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Bebee, Thomas W, Park, Juw Won, Sheridan, Katherine I, Warzecha, Claude C, Cieply, Benjamin W, Rohacek, Alex M, Xing, Yi, Carstens, Russ P·2015·eLife
DOI 10.7554/elife.08954PMC PMC4566030
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Abstract

Tissue- and cell-type-specific regulators of alternative splicing (AS) are essential components of posttranscriptional gene regulation, necessary for normal cellular function, patterning, and development. Mice with ablation of Epithelial splicing regulatory protein (Esrp1) develop cleft lip and palate. Loss of both Esrp1 and its paralog Esrp2 results in widespread developmental defects with broad implications to human disease. Deletion of the Esrps in the epidermis revealed their requirement for establishing a proper skin barrier, a primary function of epithelial cells comprising the epidermis. We profiled the global Esrp-mediated splicing regulatory program in epidermis, which revealed large-scale programs of epithelial cell-type-specific splicing required for epithelial cell functions. These mice represent a valuable model for evaluating the essential role for AS in development and function of epithelial cells, which play essential roles in tissue homeostasis in numerous organs, and provide a genetic tool to evaluate important functional properties of epithelial-specific splice variants in vivo.

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  • ESRPs are a conserved family of epithelial-specific RBPs that exert broad control over many physiological processes, including tissue regeneration and the epithelial-mesenchymal transition (EMT) during development and cancer progression.

    “ESRPs are a conserved family of epithelial-specific RBPs that exert broad control over many physiological processes, including tissue regeneration and the epithelial–mesenchymal transition (EMT) during development and cancer progression (Warzecha et al. 2010; Lu et al. 2013; Bebee et al. 2015; Derham and Kalsotra 2023).”

    From ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation (2025) · cites this paper as Bebee et al. 2015

    The Introduction describes ESRP1 and ESRP2 as epithelial-specific regulators of a genome-wide splicing program, including targets in EMT-related pathways. The Discussion describes conservation across species, and the paper supports a role in mammalian development. The passages do not establish ESRP control of tissue regeneration or cancer progression; page numbers are unavailable in our copy. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Bebee, T. W., Park, J. W., Sheridan, K. I., Warzecha, C. C., Cieply, B. W., Rohacek, A. M., Xing, Y., & Carstens, R. P.
Affiliations
  • University of Pennsylvania (US)
  • University of California, Los Angeles (US)
Corresponding author
  • Xing, Yi
  • Carstens, Russ P
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2015-09-15
Volume
4
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.08954
PMC
PMC4566030
OpenAlex
W2176968637
Cited by
161
References
6
Citations by year
2026: 8 · 2025: 16 · 2024: 20 · 2023: 13 · 2022: 13 · 2021: 21 · 2020: 23 · 2019: 12 · 2018: 9 · 2017: 13 · 2016: 12 · 2013: 1
FWCI
4.92
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of General Medical Sciences (NIGMS) (R01 GM088809, R01 GM088342, R01 GM105431)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (R56 AR066741, P30 AR057217 (sub-award), P30 AR050950 (sub-award))
  • National Institute of Dental and Craniofacial Research (NIDCR) (R56 DE024749)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (P30 DK050306 (subaward), T32DK700638, F32DK098917)
  • Alfred P. Sloan Foundation (A.P. Sloan Foundation) (Fellowship)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
ESRP1, ESRP2, alternative splicing, epithelial cells, epidermis, skin barrier, cleft lip and palate, post-transcriptional regulation, cell-type-specific splicing, developmental defects
MeSH terms
Animals, Animal Structures, Epithelial Cells, Female, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, RNA-Binding Proteins, Gene Deletion, Gene Expression Profiling

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