Rat pancreatic islet is formed by unification of multiple endocrine cell clusters

The organogenesis of islets in rat pancreas was studied by three-dimensional reconstructions from serial section micrographs. On embryonic day (E) 12, an endocrine cluster consisting mainly of glucagon-expressing cells maintained connection with the pancreatic endoderm at several regions. On E15-E17, the cluster enlarged by fusion of newly formed buds. Although the proportion of insulin-expressing cells increased, they were located in the periphery of the cluster. On the day of birth, insulin-expressing cell clusters enlarged and fused to form several cores within the islet. The glucagon-expressing cell mass expanded to form a thin mantle covering the cores. During islet organogenesis, proliferation activity was high in the exocrine duct system. Moreover, the endocrine cell clusters maintained contact with the duct epithelium throughout. We conclude that the pancreatic islet is generated by the unification of multiple endocrine clusters originated from separate regions of the duct system. The mechanism of mantle-core formation is discussed.