Source:http://linkedlifedata.com/resource/pubmed/id/12399441
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
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| pubmed:dateCreated |
2002-10-25
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| pubmed:abstractText |
The neuregulin (NRG)/epidermal growth factor (EGF) family of growth factors consists of several ligands that specifically activate four erbB receptor-tyrosine kinases, namely erbB-1 (EGF-R), erbB-2 (neu), erbB-3, and erbB-4. We have previously shown that islet morphogenesis is impaired and beta-cell differentiation delayed in mice lacking functional EGF-R [EGF-R (-/-)]. The present study aims to clarify which erbB ligands are important for islet development. Pancreatic expression of EGF, TGF-alpha, heparin-binding EGF, betacellulin (BTC), and NRG-4 was detected as early as embryonic d 13 (E13). Effects of these ligands were studied in E12.5 pancreatic explant cultures grown for 5 d ex vivo. None of the growth factors affected the ratio of endocrine to exocrine cells. However, significant effects within the endocrine cell populations were induced by EGF, BTC, and NRG-4. beta-Cell development was augmented by BTC, whereas the development of somatostatin-expressing delta-cells was stimulated by NRG-4. Both ligands decreased the numbers of glucagon-containing alpha-cells. The effect of BTC was abolished in the EGF-R (-/-) mice. A soluble erbB-4 binding fusion protein totally inhibited the effects of NRG-4 but not of BTC. Neutralization of endogenous NRG-4 activity in the model system effectively inhibited delta-cell development, indicating that this erbB4-ligand is an essential factor for delineation of the somatostatin-producing delta-cells. Our results suggest that ligands of the EGF-R/erbB-1 and erbB-4 receptors regulate the lineage determination of islet cells during pancreatic development. BTC, acting through EGF-R/erbB-1, is important for the differentiation of beta-cells. This could be applied in the targeted differentiation of stem cells into insulin-producing cells.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Neuregulins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/betacellulin,
http://linkedlifedata.com/resource/pubmed/chemical/heparin-binding EGF-like growth...,
http://linkedlifedata.com/resource/pubmed/chemical/receptor tyrosine-protein kinase...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0013-7227
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
143
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4437-46
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| pubmed:dateRevised |
2011-11-2
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| pubmed:meshHeading |
pubmed-meshheading:12399441-Animals,
pubmed-meshheading:12399441-Antibodies,
pubmed-meshheading:12399441-Cell Differentiation,
pubmed-meshheading:12399441-Epidermal Growth Factor,
pubmed-meshheading:12399441-Gene Expression,
pubmed-meshheading:12399441-Gestational Age,
pubmed-meshheading:12399441-Humans,
pubmed-meshheading:12399441-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:12399441-Islets of Langerhans,
pubmed-meshheading:12399441-Mice,
pubmed-meshheading:12399441-Mice, Knockout,
pubmed-meshheading:12399441-Neuregulins,
pubmed-meshheading:12399441-Organ Culture Techniques,
pubmed-meshheading:12399441-RNA, Messenger,
pubmed-meshheading:12399441-Receptor, Epidermal Growth Factor,
pubmed-meshheading:12399441-Recombinant Proteins,
pubmed-meshheading:12399441-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:12399441-Signal Transduction,
pubmed-meshheading:12399441-Transforming Growth Factor alpha
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| pubmed:year |
2002
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| pubmed:articleTitle |
ErbB signaling regulates lineage determination of developing pancreatic islet cells in embryonic organ culture.
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| pubmed:affiliation |
Biomedicum Helsinki, Program for Developmental and Reproductive Biology and Haartman Institute, University of Helsinki, Helsinki 00014, Finland. mari-anne.pulkkinen@helsinki.fi
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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