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Neural cell adhesion molecule (N-CAM) is required for cell type segregation and normal ultrastructure in pancreatic islets.

Esni F, Täljedal IB, Perl AK, Cremer H, Christofori G, Semb H - J. Cell Biol. (1999)

Bottom Line: These data together with the polarized distribution of islet cell nuclei and Na+/K+-ATPase indicate that islet cell polarity is also affected.Finally, degranulation of beta cells suggests that N-CAM is required for normal turnover of insulin-containing secretory granules.Taken together, our results confirm in vivo the hypothesis that a cell adhesion molecule, in this case N-CAM, is required for cell type segregation during organogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Umeå University, S-901 87 Umeå, Sweden.

ABSTRACT
Classical cell dissociation/reaggregation experiments with embryonic tissue and cultured cells have established that cellular cohesiveness, mediated by cell adhesion molecules, is important in determining the organization of cells within tissue and organs. We have employed N-CAM-deficient mice to determine whether N-CAM plays a functional role in the proper segregation of cells during the development of islets of Langerhans. In N-CAM-deficient mice the normal localization of glucagon-producing alpha cells in the periphery of pancreatic islets is lost, resulting in a more randomized cell distribution. In contrast to the expected reduction of cell-cell adhesion in N-CAM-deficient mice, a significant increase in the clustering of cadherins, F-actin, and cell-cell junctions is observed suggesting enhanced cadherin-mediated adhesion in the absence of proper N-CAM function. These data together with the polarized distribution of islet cell nuclei and Na+/K+-ATPase indicate that islet cell polarity is also affected. Finally, degranulation of beta cells suggests that N-CAM is required for normal turnover of insulin-containing secretory granules. Taken together, our results confirm in vivo the hypothesis that a cell adhesion molecule, in this case N-CAM, is required for cell type segregation during organogenesis. Possible mechanisms underlying this phenomenon may include changes in cadherin-mediated adhesion and cell polarity.

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N-CAM expression  in developing and adult pancreas. (a and b) Immunoperoxidase detection of N-CAM  (a) and PDX1 (b), a marker  for pancreatic endoderm, on  consecutive transversal sections of 9.5 dpc pancreas.  N-CAM is expressed in the  pancreatic endoderm and in  the mesenchyme, which surrounds both the ventral (vb)  and dorsal (db) pancreatic  buds. Each pancreatic bud is  indicated by a broken line. (c  and d) Double immunofluorescence staining of a transversal section of an 11.5 dpc  pancreas with polyclonal antibodies against N-CAM (c)  and glucagon (d). N-CAM is  expressed in mesenchymal  cells (m) and in clusters of α  cells (arrows), but not in  primitive epithelial cells (ep)  which are indicated by a broken line. (e and f) Double  immunofluorescence staining of 17.5 dpc pancreas with  polyclonal antibodies against  N-CAM (e) and insulin (f).  At this stage N-CAM is selectively expressed in islet-like  clusters of endocrine cells.  Exocrine tissue is indicated  by e. (g) Immunofluorescence  staining of adult pancreas with  polyclonal antibodies against  N-CAM, showing specific expression in pancreatic islets.  Exocrine tissue is indicated by  e. (h) Immunoblotting analysis  of extracts from pancreatic islets (C57) and the insulinoma  cell line βTC4 (βTC; Efrat et  al., 1988). The major N-CAM  isoform expressed in islets is  N-CAM-120. Bars, 20 μm.
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Figure 1: N-CAM expression in developing and adult pancreas. (a and b) Immunoperoxidase detection of N-CAM (a) and PDX1 (b), a marker for pancreatic endoderm, on consecutive transversal sections of 9.5 dpc pancreas. N-CAM is expressed in the pancreatic endoderm and in the mesenchyme, which surrounds both the ventral (vb) and dorsal (db) pancreatic buds. Each pancreatic bud is indicated by a broken line. (c and d) Double immunofluorescence staining of a transversal section of an 11.5 dpc pancreas with polyclonal antibodies against N-CAM (c) and glucagon (d). N-CAM is expressed in mesenchymal cells (m) and in clusters of α cells (arrows), but not in primitive epithelial cells (ep) which are indicated by a broken line. (e and f) Double immunofluorescence staining of 17.5 dpc pancreas with polyclonal antibodies against N-CAM (e) and insulin (f). At this stage N-CAM is selectively expressed in islet-like clusters of endocrine cells. Exocrine tissue is indicated by e. (g) Immunofluorescence staining of adult pancreas with polyclonal antibodies against N-CAM, showing specific expression in pancreatic islets. Exocrine tissue is indicated by e. (h) Immunoblotting analysis of extracts from pancreatic islets (C57) and the insulinoma cell line βTC4 (βTC; Efrat et al., 1988). The major N-CAM isoform expressed in islets is N-CAM-120. Bars, 20 μm.

Mentions: N-CAM's expression pattern during pancreatic development is reminiscent of its general expression pattern in the embryo, i.e., initially it is expressed more or less ubiquitously, whereas at later stages of development and in adult tissue its expression becomes more restricted. During the early stages of pancreatic ontogeny, N-CAM is expressed both in the pancreatic mesenchyme and endoderm (Fig. 1, a and b). Gradually, N-CAM becomes confined to aggregating endocrine cells (Fig. 1, c–f), which in addition to peripheral nerve endings and ganglia are the only pancreatic cells that express N-CAM in adult mice (Fig. 1 g). In contrast to pancreatic islets in the rat, which express higher levels of N-CAM in non-β cells than in β cells (Rouiller et al., 1990; Moller et al., 1992), the mouse appears to express similar levels in all endocrine cells, at least when judged by immunohistochemistry (Fig. 1 g). The predominant N-CAM polypeptide expressed in adult islets is the glycosylphosphatidylinositol-linked 120-kD isoform (Fig 1 h). In conclusion, the pattern of N-CAM expression during pancreatic organogenesis suggests an involvement in islet morphogenesis.


Neural cell adhesion molecule (N-CAM) is required for cell type segregation and normal ultrastructure in pancreatic islets.

Esni F, Täljedal IB, Perl AK, Cremer H, Christofori G, Semb H - J. Cell Biol. (1999)

N-CAM expression  in developing and adult pancreas. (a and b) Immunoperoxidase detection of N-CAM  (a) and PDX1 (b), a marker  for pancreatic endoderm, on  consecutive transversal sections of 9.5 dpc pancreas.  N-CAM is expressed in the  pancreatic endoderm and in  the mesenchyme, which surrounds both the ventral (vb)  and dorsal (db) pancreatic  buds. Each pancreatic bud is  indicated by a broken line. (c  and d) Double immunofluorescence staining of a transversal section of an 11.5 dpc  pancreas with polyclonal antibodies against N-CAM (c)  and glucagon (d). N-CAM is  expressed in mesenchymal  cells (m) and in clusters of α  cells (arrows), but not in  primitive epithelial cells (ep)  which are indicated by a broken line. (e and f) Double  immunofluorescence staining of 17.5 dpc pancreas with  polyclonal antibodies against  N-CAM (e) and insulin (f).  At this stage N-CAM is selectively expressed in islet-like  clusters of endocrine cells.  Exocrine tissue is indicated  by e. (g) Immunofluorescence  staining of adult pancreas with  polyclonal antibodies against  N-CAM, showing specific expression in pancreatic islets.  Exocrine tissue is indicated by  e. (h) Immunoblotting analysis  of extracts from pancreatic islets (C57) and the insulinoma  cell line βTC4 (βTC; Efrat et  al., 1988). The major N-CAM  isoform expressed in islets is  N-CAM-120. Bars, 20 μm.
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Related In: Results  -  Collection

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Figure 1: N-CAM expression in developing and adult pancreas. (a and b) Immunoperoxidase detection of N-CAM (a) and PDX1 (b), a marker for pancreatic endoderm, on consecutive transversal sections of 9.5 dpc pancreas. N-CAM is expressed in the pancreatic endoderm and in the mesenchyme, which surrounds both the ventral (vb) and dorsal (db) pancreatic buds. Each pancreatic bud is indicated by a broken line. (c and d) Double immunofluorescence staining of a transversal section of an 11.5 dpc pancreas with polyclonal antibodies against N-CAM (c) and glucagon (d). N-CAM is expressed in mesenchymal cells (m) and in clusters of α cells (arrows), but not in primitive epithelial cells (ep) which are indicated by a broken line. (e and f) Double immunofluorescence staining of 17.5 dpc pancreas with polyclonal antibodies against N-CAM (e) and insulin (f). At this stage N-CAM is selectively expressed in islet-like clusters of endocrine cells. Exocrine tissue is indicated by e. (g) Immunofluorescence staining of adult pancreas with polyclonal antibodies against N-CAM, showing specific expression in pancreatic islets. Exocrine tissue is indicated by e. (h) Immunoblotting analysis of extracts from pancreatic islets (C57) and the insulinoma cell line βTC4 (βTC; Efrat et al., 1988). The major N-CAM isoform expressed in islets is N-CAM-120. Bars, 20 μm.
Mentions: N-CAM's expression pattern during pancreatic development is reminiscent of its general expression pattern in the embryo, i.e., initially it is expressed more or less ubiquitously, whereas at later stages of development and in adult tissue its expression becomes more restricted. During the early stages of pancreatic ontogeny, N-CAM is expressed both in the pancreatic mesenchyme and endoderm (Fig. 1, a and b). Gradually, N-CAM becomes confined to aggregating endocrine cells (Fig. 1, c–f), which in addition to peripheral nerve endings and ganglia are the only pancreatic cells that express N-CAM in adult mice (Fig. 1 g). In contrast to pancreatic islets in the rat, which express higher levels of N-CAM in non-β cells than in β cells (Rouiller et al., 1990; Moller et al., 1992), the mouse appears to express similar levels in all endocrine cells, at least when judged by immunohistochemistry (Fig. 1 g). The predominant N-CAM polypeptide expressed in adult islets is the glycosylphosphatidylinositol-linked 120-kD isoform (Fig 1 h). In conclusion, the pattern of N-CAM expression during pancreatic organogenesis suggests an involvement in islet morphogenesis.

Bottom Line: These data together with the polarized distribution of islet cell nuclei and Na+/K+-ATPase indicate that islet cell polarity is also affected.Finally, degranulation of beta cells suggests that N-CAM is required for normal turnover of insulin-containing secretory granules.Taken together, our results confirm in vivo the hypothesis that a cell adhesion molecule, in this case N-CAM, is required for cell type segregation during organogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Umeå University, S-901 87 Umeå, Sweden.

ABSTRACT
Classical cell dissociation/reaggregation experiments with embryonic tissue and cultured cells have established that cellular cohesiveness, mediated by cell adhesion molecules, is important in determining the organization of cells within tissue and organs. We have employed N-CAM-deficient mice to determine whether N-CAM plays a functional role in the proper segregation of cells during the development of islets of Langerhans. In N-CAM-deficient mice the normal localization of glucagon-producing alpha cells in the periphery of pancreatic islets is lost, resulting in a more randomized cell distribution. In contrast to the expected reduction of cell-cell adhesion in N-CAM-deficient mice, a significant increase in the clustering of cadherins, F-actin, and cell-cell junctions is observed suggesting enhanced cadherin-mediated adhesion in the absence of proper N-CAM function. These data together with the polarized distribution of islet cell nuclei and Na+/K+-ATPase indicate that islet cell polarity is also affected. Finally, degranulation of beta cells suggests that N-CAM is required for normal turnover of insulin-containing secretory granules. Taken together, our results confirm in vivo the hypothesis that a cell adhesion molecule, in this case N-CAM, is required for cell type segregation during organogenesis. Possible mechanisms underlying this phenomenon may include changes in cadherin-mediated adhesion and cell polarity.

Show MeSH
Related in: MedlinePlus