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J. Cell Biol.,
Volume 144, Number 2, January 25, 1999 325-337
* Department of Microbiology and 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 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
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 
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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