Advance Publication Acta Histochem. Cytochem. 45 (1): 65–75, 2012 doi:10.1267/ahc.11052 J01TRAa03oecHp.4kgt1a1Ca47yu2n1-olH65a0S,7r98i5oJs/902Aatc10ohpirecattih.ncy1el1meo0fi5cH2a iestoCchyetomcihsetrmyicaand Cytochemistry Temporal and Spatial Cellular Distribution of Neural Crest Derivatives and Alpha Cells during Islet Development Kousuke Shimada1, Toshiaki Tachibana1, Kei Fujimoto2, Takashi Sasaki2,3 and Masataka Okabe1 1Department of Anatomy, The Jikei University School of Medicine, 3–25–8 Nishishinbashi, Minato-ku, Tokyo 105–8461, Japan, 2Division of Diabetes and Endocrinology, The Jikei University School of Medicine, 3–25–8 Nishishinbashi, Minato-ku, Tokyo 105–8461, Japan and 3Institute of Clinical Medicine and Research, The Jikei University School of Medicine, 163–1 Kashiwashita, Kashiwa, Chiba 277–8567, Japan 00 Received October 31, 2011; accepted December 19, 2011; published online February 15, 2012 © 201R2ecTehnet sJatupdaniesSohcaievtey roefveHailsetdocthheamt isstirgynaalnsdfrom neural crest (NC) derivatives regulate the mass, proliferation, and maturation of beta cells in developing fetal pancreas. However, little is known about the cellular distribution of NC derivatives during pancreatic development or the process whereby the developing islets are enclosed. We studied the temporal and spatial distribution of NC derivatives and endocrine cells at each developmental stage. At embryonic day 10.5 (E10.5) of mouse embryo, NC derivatives that migrated to the prospective pancreatic region were distributed in close proximity to pancreatic epithelial cells. As development advanced, most NC derivatives progressively surrounded endocrine rather than exocrine cells, and were distributed in closer proximity to alpha cells rather than to beta cells. At E20, approximately 70% of the NC derivatives enclosing endocrine cells were distributed in close proximity to alpha cells. Moreover, the expression of SynCAM, a Ca2+-independent homophilic trans-cell adhesion molecule, was confirmed from E16.5 on and was more remarkable at the cell boundaries of alpha cells and NC derivatives. These findings suggest that NC derivatives might be distributed in close proximity to alpha cells as a result of homophilic binding of SynCAM expressed by alpha cells and NC derivatives during islet development. Key words: neural crest, alpha cells, CADM-1 (SynCAM), islet development I. Introduction Islets of Langerhans are not just endocrine cell clusters composed of alpha and beta cells, but comprise part of an ectodermally-derived nervous system known to innervate the islets during cell development in pancreas. It is therefore presumed that the islets are multicellular complexes com- prising endocrine cells that form aggregates with nervous system components [25, 31], and constitute higher-order endocrine units that maintain nutritional and blood glucose homeostasis. Nerve signals are known to improve the Correspondence to: Masataka Okabe, M.D., Ph.D., Department of Anatomy, The Jikei University School of Medicine, 3–25–8 Nishishinbashi, Minato-ku, Tokyo 105–8461, Japan. E-mail: maokabe@jikei.ac.jp function of endocrine cells in adults [6, 11, 18, 26], but the detailed functions of the ectodermally-derived cells enclos- ing pancreatic islets, such as the functions of glial fibrillary acidic protein (GFAP)- and S100-positive peri-islet Schwann cells (PISCs) that surround nerve fibers around the islets [5, 30, 34, 37], remain to be investigated. Although the functional significance of PISCs in endocrine cells in adults remains unclear, it is presumed that nerve-related cells associated with the islets play a key role in protecting the islets for the following reasons: (1) they are the first target of the pathogenesis of type 1 diabetes, (2) their disruption leads to a pathogenic cascade [36, 39], and (3) in a murine model of islet injury type 2 diabetes, the PISCs of mice treated with streptozotocin displayed reactive gliosis [35]. The first morphological indications of pancreatic formation are observed around embryonic day 9.5 (E9.5) of © 2012 The Japan Society of Histochemistry and Cytochemistry