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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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Histological analysis of adult wild-type and  N-CAM-deficient pancreata.  (a–d) Hematoxylin-eosin  stainings of paraffin sections  of control (a and c, +/+) and  N-CAM −/− (b and d, −/−)  mice. Based on hematoxylin-eosin stainings, pancreata of  N-CAM-deficient mice appear normal (data not shown  for N-CAM +/− pancreata).  (e-g) Immunofluorescence  stainings of sections from  adult wild-type (e, +/+),  N-CAM +/− (f, +/−), and  N-CAM −/− (g, −/−) pancreata with anti-N-CAM  polyclonal antibodies. (h)  Immunoblotting analysis of  pancreatic islet extracts from  wild-type (+/+), heterozygous (+/−), and homozygous (−/−) animals, using  anti-N-CAM polyclonal  antibodies. While N-CAM  is completely absent in  N-CAM −/− islets, N-CAM  +/− islets express ∼50% of  wild-type islets. Bars: (a, b,  and e–g) 20 μm; (c and d)  10 μm.
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Figure 2: Histological analysis of adult wild-type and N-CAM-deficient pancreata. (a–d) Hematoxylin-eosin stainings of paraffin sections of control (a and c, +/+) and N-CAM −/− (b and d, −/−) mice. Based on hematoxylin-eosin stainings, pancreata of N-CAM-deficient mice appear normal (data not shown for N-CAM +/− pancreata). (e-g) Immunofluorescence stainings of sections from adult wild-type (e, +/+), N-CAM +/− (f, +/−), and N-CAM −/− (g, −/−) pancreata with anti-N-CAM polyclonal antibodies. (h) Immunoblotting analysis of pancreatic islet extracts from wild-type (+/+), heterozygous (+/−), and homozygous (−/−) animals, using anti-N-CAM polyclonal antibodies. While N-CAM is completely absent in N-CAM −/− islets, N-CAM +/− islets express ∼50% of wild-type islets. Bars: (a, b, and e–g) 20 μm; (c and d) 10 μm.

Mentions: Control (+/+), N-CAM heterozygous (+/−), and N-CAM homozygous (−/−) mutant mice in a C57Bl/6J background were used (Cremer et al., 1994). Control experiments demonstrated that no N-CAM protein is expressed in the pancreas of N-CAM −/− mice (see Fig. 2).


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)

Histological analysis of adult wild-type and  N-CAM-deficient pancreata.  (a–d) Hematoxylin-eosin  stainings of paraffin sections  of control (a and c, +/+) and  N-CAM −/− (b and d, −/−)  mice. Based on hematoxylin-eosin stainings, pancreata of  N-CAM-deficient mice appear normal (data not shown  for N-CAM +/− pancreata).  (e-g) Immunofluorescence  stainings of sections from  adult wild-type (e, +/+),  N-CAM +/− (f, +/−), and  N-CAM −/− (g, −/−) pancreata with anti-N-CAM  polyclonal antibodies. (h)  Immunoblotting analysis of  pancreatic islet extracts from  wild-type (+/+), heterozygous (+/−), and homozygous (−/−) animals, using  anti-N-CAM polyclonal  antibodies. While N-CAM  is completely absent in  N-CAM −/− islets, N-CAM  +/− islets express ∼50% of  wild-type islets. Bars: (a, b,  and e–g) 20 μm; (c and d)  10 μm.
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Related In: Results  -  Collection

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Figure 2: Histological analysis of adult wild-type and N-CAM-deficient pancreata. (a–d) Hematoxylin-eosin stainings of paraffin sections of control (a and c, +/+) and N-CAM −/− (b and d, −/−) mice. Based on hematoxylin-eosin stainings, pancreata of N-CAM-deficient mice appear normal (data not shown for N-CAM +/− pancreata). (e-g) Immunofluorescence stainings of sections from adult wild-type (e, +/+), N-CAM +/− (f, +/−), and N-CAM −/− (g, −/−) pancreata with anti-N-CAM polyclonal antibodies. (h) Immunoblotting analysis of pancreatic islet extracts from wild-type (+/+), heterozygous (+/−), and homozygous (−/−) animals, using anti-N-CAM polyclonal antibodies. While N-CAM is completely absent in N-CAM −/− islets, N-CAM +/− islets express ∼50% of wild-type islets. Bars: (a, b, and e–g) 20 μm; (c and d) 10 μm.
Mentions: Control (+/+), N-CAM heterozygous (+/−), and N-CAM homozygous (−/−) mutant mice in a C57Bl/6J background were used (Cremer et al., 1994). Control experiments demonstrated that no N-CAM protein is expressed in the pancreas of N-CAM −/− mice (see Fig. 2).

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