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Precursor cells of mouse endocrine pancreas coexpress insulin, glucagon and the neuronal proteins tyrosine hydroxylase and neuropeptide Y, but not pancreatic polypeptide
G. Teitelman, S. Alpert, J.M. Polak, A. Martinez, D. Hanahan
Development 1993 118: 1031-1039;

Summary

The early progenitor cells to the pancreatic islets in the mouse have been characterized so as to re-examine their possible lineage relationships to the four islet cell types found in mature islets. Insulin and glucagon were both first expressed at embryonic day 9.5, and many cells coexpressed these two markers, as shown by light and electron microscopic analysis using double-label immunohistochemistry. Incubation of embryonic pancreas with 1% glutaraldehyde, a fixative commonly used by electron microscopists, abolished this reactivity, thereby explaining reported difficulties in detecting these precursor cells. Using antisera specific for neuropeptide Y (NPY) a peptide with considerable homology to pancreatic polypeptide (PP), we show that NPY first appears with insulin and glucagon immunoreactivity at E9.5, and is co-expressed with glucagon in a majority of adult alpha cells. As we have previously reported, PP itself is first detectable immunocytochemically at postnatal day 1 with PP-specific antibodies. However, antibodies raised against bovine PP are shown by dot blotting to recognize NPY with comparable avidity, indicating that a recent report of islet progenitor cells containing PP at E9.5 (Herrera, P. L., Huarte, J., Sanvito, F., Meda, P., Orci, L. and Vassalli, J. D. (1991) Development 113, 1257–1265), actually represents cross-reactivity to NPY. The data support a model in which early precursor cells to the endocrine pancreas co-activate and co-express a set of islet cell hormone and neural genes, whose expression is both selectively increased and extinguished as development proceeds, concomitant with a restriction to the patterns of expression characteristic of mature islet cell types.

Reference

    1. Adkins B.,
    2. Muller C.,
    3. Okada C. Y.,
    4. Reicert R. A.,
    5. Weissman I. L.,
    6. Spangrude J.
    (1987) Early events in T cell maturation. Ann Rev. Immunol 5, 535–621
    OpenUrl
    1. Alpert S.,
    2. Hanahan D.,
    3. Teitelman G.
    (1988) Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons. Cell 53, 295–308
    OpenUrlCrossRefPubMedWeb of Science
    1. Ali-Rachedi A.,
    2. Varndell I. M.,
    3. Adrian T. E.,
    4. Gapp D. A.,
    5. Van Noorden S.,
    6. Bloom S. R.,
    7. Polak J. M.
    (1984) Peptide YY (PYY) immunoreactivity is co-stored with glucagon-related immunoreactants in endocrine cells of the gut and pancreas. Histochemistry 80, 487–491
    OpenUrlCrossRefPubMedWeb of Science
    1. De Krijger R. R.,
    2. Aanstoot H. J.,
    3. Kranenburg G.,
    4. Reinhard M.,
    5. Visser W. J.,
    6. Bruining G. J.
    (1992) The midgestational human fetal pancreas contains cells co-expressing islet hormones. Dev. Biol 153, 368–375
    OpenUrlCrossRefPubMedWeb of Science
    1. DiMaggio D. A.,
    2. Chronwall B. M.,
    3. Buchanan K.,
    4. O'Donohue T. L.
    (1985) Pancreatic polypeptide immunoreactivity in brain is actually neuropeptide Y. Neuroscience 15, 1149–1157
    OpenUrlCrossRefPubMed
    1. Gittes G. K.,
    2. Rutter W. J.
    (1992) Onset of cell-specific gene expression in the developing mouse pancreas. Proc. Natl. Acad. Sci. USA 89, 1128–1132
    OpenUrlAbstract/FREE Full Text
    1. Guidos C. J.,
    2. Weissman I. L.,
    3. Adkins B.
    (1989) Intrathymic maturation of murine T lymphocytes from CD-8 precursors. Proc. Natl. Acad. Sci. USA 86, 7582–7587
    OpenUrl
    1. Han J. H.,
    2. Rall L.,
    3. Rutter W. J.
    (1986) Selective expression of rat pancreatic genes during embryonic development. Proc. Natl. Acad. Sci. USA 83, 110–114
    OpenUrlAbstract/FREE Full Text
    1. Herrera P. L.,
    2. Huarte J.,
    3. Sanvito F.,
    4. Meda P.,
    5. Orci L.,
    6. Vassalli J. D.
    (1991) Embryogenesis of the murine endocrine pancreas; early expression of the pancreatic polypeptide gene. Development 113, 1257–1265
    OpenUrlAbstract
    1. Larsson L. I.
    (1981) A novel immunocytochemical model system for specificity and sensitivity screening of antisera against multiple antigens. J. Histochem. Cytochem 29, 408–410
    OpenUrlAbstract/FREE Full Text
    1. Lukinius A.,
    2. Ericsson J. L. E.,
    3. Grimelius L.,
    4. Korsgren O.
    (1992) Electron microscopic immunocytochemical study of the ontogeny of fetal human and porcine endocrine pancreas, with special reference to co-localization of the four major islet hormones. Dev. Biol 153, 376–390
    OpenUrlCrossRefPubMed
    1. Pickel V. M.,
    2. Chan J.,
    3. Milner T.
    (1985) Autoradiographic detection of125- IgG labelled secondary antiserum. A sensitive light and electron microscope labeling method compatible with peroxidase for dual localization of neuronal antigens. J. Histochem. Cytochem 34, 707–718
    OpenUrl
    1. Raff M. C.
    (1989) Glial cell diversification in the rat optic nerve. Science 243, 1450–1455
    OpenUrlAbstract/FREE Full Text
    1. Sundler F.,
    2. Hakanson R.,
    3. Larsson L. I.
    (1977) Ontogeny of rat pancreatic polypeptide (PP) cells. Cell Tissue Res 178, 303–306
    OpenUrlPubMed
    1. Tatemoto K.,
    2. Carlquist M.,
    3. Mutt V.
    (1982) Neuropeptide Y, a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature 296, 659–660
    OpenUrlCrossRefPubMed
    1. Teitelman G.,
    2. Joh T. H.,
    3. Reis D. J.
    (1981) Transformation of catecholaminergic precursors into glucagon (A) cells in mouse embryonic pancreas. Proc. Natl. Acad. Sci. USA 78, 5225–5229
    OpenUrlAbstract/FREE Full Text
    1. Teitelman G.,
    2. Lee J. K.,
    3. Alpert S.
    (1987) Expression of cell type- specific markers during pancreatic development in the mouse, implications for pancreatic cell lineages. Cell Tissue Res 250, 435–439
    OpenUrlPubMed
    1. Teitelman G.,
    2. Lee J. K.
    (1987) Cell lineage analysis of pancreatic islet cell development, glucagon and insulin cells arise from catecholaminergic precursors present in the pancreatic duct. Dev. Biol 121, 454–466
    OpenUrlCrossRefPubMedWeb of Science
    1. Varndell I. M.,
    2. Tapia F. J.,
    3. Probert L.,
    4. Buchan A. M. J.,
    5. Gu J.,
    6. De Mey J.,
    7. Bloom S. R.,
    8. Polak J. M.
    (1982) Immunogold staining procedure for the localization of regulatory peptides. Peptides 3, 259–272
    OpenUrlCrossRefPubMed
    1. Wentworth B. M.,
    2. Schaefer I. M.,
    3. Villa Komaroff L.,
    4. Chirgwin J. M.
    (1986) Characterization of the two nonallelic genes encoding mouse preproinsulin. J. Mol. Evol 23, 305–312
    OpenUrlCrossRefPubMedWeb of Science
    1. Wessels N. K.,
    2. Evans J.
    (1968) Ultrastructural studies of early morphogenesis and cytodifferentiation in the embryonic mammalian pancreas. Dev. Biol 17, 413–446
    OpenUrlCrossRefPubMedWeb of Science
    1. Yoshinari M.,
    2. Daikoku S.
    (1982) Ontogenic appearance of immunoreactive endocrine cells in rat pancreatic islets. Anat. Embryol 165, 63–70
    OpenUrlCrossRefPubMed
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JOURNAL ARTICLES
Precursor cells of mouse endocrine pancreas coexpress insulin, glucagon and the neuronal proteins tyrosine hydroxylase and neuropeptide Y, but not pancreatic polypeptide
G. Teitelman, S. Alpert, J.M. Polak, A. Martinez, D. Hanahan
Development 1993 118: 1031-1039;
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