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Planar cell polarity (PCP) refers to the collective orientation of cells within the epithelial plane. We show that progenitor cells forming the ducts of the embryonic pancreas express PCP proteins and exhibit an active PCP pathway. Planar polarity proteins are acquired at embryonic day 11.5 synchronously to apicobasal polarization of pancreas progenitors. Loss of function of the two PCP core components Celsr2 and Celsr3 shows that they control the differentiation of endocrine cells from polarized progenitors, with a prevalent effect on insulin-producing beta cells. This results in a decreased glucose clearance. Loss of Celsr2 and 3 leads to a reduction of Jun phosphorylation in progenitors, which, in turn, reduces beta cell differentiation from endocrine progenitors. These results highlight the importance of the PCP pathway in cell differentiation in vertebrates. In addition, they reveal that tridimensional organization and collective communication of cells are needed in the pancreatic epithelium in order to generate appropriate numbers of endocrine cells.
Pubmed ID: 23177622
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THIS RESOURCE IS NO LONGER IN SERVICE, documented May 10, 2017. A pilot effort that has developed a centralized, web-based biospecimen locator that presents biospecimens collected and stored at participating Arizona hospitals and biospecimen banks, which are available for acquisition and use by researchers. Researchers may use this site to browse, search and request biospecimens to use in qualified studies. The development of the ABL was guided by the Arizona Biospecimen Consortium (ABC), a consortium of hospitals and medical centers in the Phoenix area, and is now being piloted by this Consortium under the direction of ABRC. You may browse by type (cells, fluid, molecular, tissue) or disease. Common data elements decided by the ABC Standards Committee, based on data elements on the National Cancer Institute''s (NCI''s) Common Biorepository Model (CBM), are displayed. These describe the minimum set of data elements that the NCI determined were most important for a researcher to see about a biospecimen. The ABL currently does not display information on whether or not clinical data is available to accompany the biospecimens. However, a requester has the ability to solicit clinical data in the request. Once a request is approved, the biospecimen provider will contact the requester to discuss the request (and the requester''s questions) before finalizing the invoice and shipment. The ABL is available to the public to browse. In order to request biospecimens from the ABL, the researcher will be required to submit the requested required information. Upon submission of the information, shipment of the requested biospecimen(s) will be dependent on the scientific and institutional review approval. Account required. Registration is open to everyone., documented on August 1, 2015. Consortium that aims to facilitate interdisciplinary collaborations to advance the understanding of pancreatic islet development and function, with the goal of developing innovative therapies to correct the loss of beta cell mass in diabetes, including cell reprogramming, regeneration and replacement. They are responsible for collaboratively generating the necessary reagents, mouse strains, antibodies, assays, protocols, technologies and validation assays that are beyond the scope of any single research effort. The scientific goals for the BCBC are to: * Use cues from pancreatic development to directly differentiate pancreatic beta cells and islets from stem / progenitor cells for use in cell-replacement therapies for diabetes, * Determine how to stimulate beta cell regeneration in the adult pancreas as a basis for improving beta cell mass in diabetic patients, * Determine how to reprogram progenitor / adult cells into pancreatic beta-cells both in-vitro and in-vivo as a mean for developing cell-replacement therapies for diabetes, and * Investigate the progression of human type-1 diabetes using patient-derived cells and tissues transplanted in humanized mouse models. Many of the BCBC investigator-initiated projects involve reagent-generating activities that will benefit the larger scientific community. The combination of programs and activities should accelerate the pace of major new discoveries and progress within the field of beta cell biology.
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