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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-deficient  mice exhibit ultrastructural  alterations in islet cells. Electron photomicrographs of islets from control (a, +/+)  and homozygous (b–d, −/−)  animals. Because the ultrastructural changes were the  same in heterozygous and  homozygous mutants, only  the data from the homozygous mice is shown. In b, and  at higher magnification in c,  clustering of cell–cell junctions, including desmosomes  (arrowheads in c) and adherens type junctions (brackets in c), between four β cells  are shown. In b three β cells  contain a diminished number  of secretory granules. Arrows in b-d indicate accumulation of residual bodies. In d  residual bodies contain secretory granules. Dilation of  rough endoplasmic reticulum  was observed in β cells (asterisks in c) and α cells (data  not shown). Bars: (a) 1 μm;  (b) 2 μm; (c and d) 0.5 μm.
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Figure 6: N-CAM-deficient mice exhibit ultrastructural alterations in islet cells. Electron photomicrographs of islets from control (a, +/+) and homozygous (b–d, −/−) animals. Because the ultrastructural changes were the same in heterozygous and homozygous mutants, only the data from the homozygous mice is shown. In b, and at higher magnification in c, clustering of cell–cell junctions, including desmosomes (arrowheads in c) and adherens type junctions (brackets in c), between four β cells are shown. In b three β cells contain a diminished number of secretory granules. Arrows in b-d indicate accumulation of residual bodies. In d residual bodies contain secretory granules. Dilation of rough endoplasmic reticulum was observed in β cells (asterisks in c) and α cells (data not shown). Bars: (a) 1 μm; (b) 2 μm; (c and d) 0.5 μm.

Mentions: Changes in cell–cell interactions and in cellular sorting may also affect intracellular organization and possibly physiological functions of a cell. To investigate this possibility we analyzed islets of Langerhans of control mice and N-CAM-deficient mice by transmission electron microscopy. Although in both N-CAM +/− and N-CAM −/− animals the majority of endocrine cells appeared morphologically normal, a significant fraction of β cells and α cells appeared ultrastructurally perturbed. The reorganization of cadherins and F-actin as seen by light microscopy (Fig. 4) appears to correlate with the accumulation of cell–cell junctions in multicellular endocrine structures (Fig. 6, b and c). Although each of these junctions, including desmosomes and adherens type junctions, are found scattered in islet cell contacts of control mice, they appear to accumulate towards the center of groups of cells in islets of N-CAM-deficient mice (Fig. 6, b and c). Moreover, a significant fraction of β cells contained a diminished number of secretory granules (Fig. 6, compare a to b) together with an increased number of residual bodies that are frequently associated with the plasma membrane (Fig. 6, b–d). Secretory granules were occasionally observed within residual bodies (Fig. 6 d), suggesting increased autophagy. Dilation of the rough endoplasmic reticulum was seen in both β cells and α cells (Fig. 6 c, and data not shown). As the corresponding changes were not observed in control mice, it appears that N-CAM-mediated cell–cell interactions are required for organizing islet cell–cell contacts, as well as for maintaining normal activity and turnover of organelles within islet cells.


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-deficient  mice exhibit ultrastructural  alterations in islet cells. Electron photomicrographs of islets from control (a, +/+)  and homozygous (b–d, −/−)  animals. Because the ultrastructural changes were the  same in heterozygous and  homozygous mutants, only  the data from the homozygous mice is shown. In b, and  at higher magnification in c,  clustering of cell–cell junctions, including desmosomes  (arrowheads in c) and adherens type junctions (brackets in c), between four β cells  are shown. In b three β cells  contain a diminished number  of secretory granules. Arrows in b-d indicate accumulation of residual bodies. In d  residual bodies contain secretory granules. Dilation of  rough endoplasmic reticulum  was observed in β cells (asterisks in c) and α cells (data  not shown). Bars: (a) 1 μm;  (b) 2 μm; (c and d) 0.5 μm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2132899&req=5

Figure 6: N-CAM-deficient mice exhibit ultrastructural alterations in islet cells. Electron photomicrographs of islets from control (a, +/+) and homozygous (b–d, −/−) animals. Because the ultrastructural changes were the same in heterozygous and homozygous mutants, only the data from the homozygous mice is shown. In b, and at higher magnification in c, clustering of cell–cell junctions, including desmosomes (arrowheads in c) and adherens type junctions (brackets in c), between four β cells are shown. In b three β cells contain a diminished number of secretory granules. Arrows in b-d indicate accumulation of residual bodies. In d residual bodies contain secretory granules. Dilation of rough endoplasmic reticulum was observed in β cells (asterisks in c) and α cells (data not shown). Bars: (a) 1 μm; (b) 2 μm; (c and d) 0.5 μm.
Mentions: Changes in cell–cell interactions and in cellular sorting may also affect intracellular organization and possibly physiological functions of a cell. To investigate this possibility we analyzed islets of Langerhans of control mice and N-CAM-deficient mice by transmission electron microscopy. Although in both N-CAM +/− and N-CAM −/− animals the majority of endocrine cells appeared morphologically normal, a significant fraction of β cells and α cells appeared ultrastructurally perturbed. The reorganization of cadherins and F-actin as seen by light microscopy (Fig. 4) appears to correlate with the accumulation of cell–cell junctions in multicellular endocrine structures (Fig. 6, b and c). Although each of these junctions, including desmosomes and adherens type junctions, are found scattered in islet cell contacts of control mice, they appear to accumulate towards the center of groups of cells in islets of N-CAM-deficient mice (Fig. 6, b and c). Moreover, a significant fraction of β cells contained a diminished number of secretory granules (Fig. 6, compare a to b) together with an increased number of residual bodies that are frequently associated with the plasma membrane (Fig. 6, b–d). Secretory granules were occasionally observed within residual bodies (Fig. 6 d), suggesting increased autophagy. Dilation of the rough endoplasmic reticulum was seen in both β cells and α cells (Fig. 6 c, and data not shown). As the corresponding changes were not observed in control mice, it appears that N-CAM-mediated cell–cell interactions are required for organizing islet cell–cell contacts, as well as for maintaining normal activity and turnover of organelles within islet cells.

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