ArticleDevelopment (Cambridge, England)2011
The Cdk4-E2f1 pathway regulates early pancreas development by targeting Pdx1+ progenitors and Ngn3+ endocrine precursors.
Article in Development (Cambridge, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
29 citing papers in PubMed, 57 citations in OpenAlex.
- Epigenetic memory as crucial contributing factor in directing the differentiation of human iPSC into pancreatic β-cells in vitro.Cell and tissue research · 2025Review
- 3D model of mouse embryonic pancreas and endocrine compartment using stem cell-derived mesoderm and pancreatic progenitors.iScience · 2024Article
- E2F transcription factors promote tumorigenicity in pancreatic ductal adenocarcinoma.Cancer medicine · 2024Article
- CDK4-E2F3 signals enhance oxidative skeletal muscle fiber numbers and function to affect myogenesis and metabolism.The Journal of clinical investigation · 2023Article
- Chemical inhibitors of cyclin-dependent kinase (CDKi) improve pancreatic endocrine differentiation of iPS cells.In vitro cellular & developmental biology. Animal · 2023Article
- Recovering false negatives in CRISPR fitness screens with JLOE.Nucleic acids research · 2023Article
- TRPM7 kinase is required for insulin production and compensatory islet responses during obesity.JCI insight · 2023Article
- Article
- TGF-β Signaling in Pancreatic Islet β Cell Development and Function.Endocrinology · 2021Review
- Cinnamaldehyde Improves Metabolic Functions in Streptozotocin-Induced Diabetic Mice by Regulating Gut Microbiota.Drug design, development and therapy · 2021Article
- Oncogenic miR-20b-5p contributes to malignant behaviors of breast cancer stem cells by bidirectionally regulating CCND1 and E2F1.BMC cancer · 2020Article
- E2F1 Mediates the Retinoic Acid-Induced Transcription ofMolecular and cellular biology · 2018Article
- Phosphorylation of NEUROG3 Links Endocrine Differentiation to the Cell Cycle in Pancreatic Progenitors.Developmental cell · 2017Article
- Loss of Cyclin-dependent Kinase 2 in the Pancreas Links Primary β-Cell Dysfunction to Progressive Depletion of β-Cell Mass and Diabetes.The Journal of biological chemistry · 2017Article
- E2F1, a Novel Regulator of Metabolism.Frontiers in endocrinology · 2017Review
- Association of polymorphic markers of genesPeerJ · 2017Article
- Initiation of stem cell differentiation involves cell cycle-dependent regulation of developmental genes by Cyclin D.Genes & development · 2016Article
- The cell cycle as a brake for β-cell regeneration from embryonic stem cells.Stem cell research & therapy · 2016Review
- Notch Signaling in Pancreatic Development.International journal of molecular sciences · 2015Review
- Transcriptional control of stem cell fate by E2Fs and pocket proteins.Frontiers in genetics · 2015Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Cell division and cell differentiation are intricately regulated processes vital to organ development. Cyclin-dependent kinases (Cdks) are master regulators of the cell cycle that orchestrate the cell division and differentiation programs. Cdk1 is essential to drive cell division and is required for the first embryonic divisions, whereas Cdks 2, 4 and 6 are dispensable for organogenesis but vital for tissue-specific cell development. Here, we illustrate an important role for Cdk4 in regulating early pancreas development. Pancreatic development involves extensive morphogenesis, proliferation and differentiation of the epithelium to give rise to the distinct cell lineages of the adult pancreas. The cell cycle molecules that specify lineage commitment within the early pancreas are unknown. We show that Cdk4 and its downstream transcription factor E2f1 regulate mouse pancreas development prior to and during the secondary transition. Cdk4 deficiency reduces embryonic pancreas size owing to impaired mesenchyme development and fewer Pdx1(+) pancreatic progenitor cells. Expression of activated Cdk4(R24C) kinase leads to increased Nkx2.2(+) and Nkx6.1(+) cells and a rise in the number and proliferation of Ngn3(+) endocrine precursors, resulting in expansion of the β cell lineage. We show that E2f1 binds and activates the Ngn3 promoter to modulate Ngn3 expression levels in the embryonic pancreas in a Cdk4-dependent manner. These results suggest that Cdk4 promotes β cell development by directing E2f1-mediated activation of Ngn3 and increasing the pool of endocrine precursors, and identify Cdk4 as an important regulator of early pancreas development that modulates the proliferation potential of pancreatic progenitors and endocrine precursors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.