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© The Rockefeller University Press, 0021-9525/1999//325 $5.00
The Journal of Cell Biology, Volume 144, Number 2, , 1999 325-337

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Neural Cell Adhesion Molecule (N-CAM) Is Required for Cell Type Segregation and Normal Ultrastructure in Pancreatic Islets



Farzad Esni*, Inge-Bert Täljedal{ddagger}, Anne-Karina Perl§, Harold Cremer||, Gerhard Christofori§, and Henrik Semb*

* Department of Microbiology and {ddagger} Department of Histology and Cell Biology, Umeå University, S-901 87 Umeå, Sweden; § Research Institute of Molecular Pathology, A-1030 Vienna, Austria; and || Developmental Biology Institute of Marseille, University de Mediterranee, CNRS/INSERM, Campus de Luminy, 13288 Marseille cedex 09, France

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 β 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.

Key Words: N-CAM • knockout • pancreas • cadherin • organogenesis

Abbreviations used in this paper: CAMs, cell adhesion molecules; Cy3, indocarbocyanine; dpc, days postcoitum; eGFP, enhanced green fluorescence protein; N-CAM, neural cell adhesion molecule.

Address correspondence to Henrik Semb at Institute of Medical Biochemistry, Göteborg University, Box 440, S-405 30 Göteborg, Sweden, Tel.: 46 31 773 3779. Fax: 46 31 41 61 08. E-mail: henrik.semb{at}medkem.gu.se


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