Budding, fission, and fusion: Unveiling patterns shaping pancreatic islet size and distribution in squamate reptiles

A growing body of evidence suggests that lizards are promising model organisms for studying various developmental processes. However, knowledge of pancreatic islet distribution in non-ophidian squamates remains limited. The most comprehensive accounts available to date lack three-dimensional reconstructions and often show inconsistencies. In this study, we aimed to address both aspects: first, by evaluating squamate embryos as model systems for understanding general mechanisms of pancreatic islet morphogenesis in vertebrates, and second, by conducting a comparative analysis of islet development in squamates from an evolutionary perspective. In this study, we analyzed embryos of four non-ophidian squamates representing three major evolutionary lineages: Iguania-the brown anole Anolis sagrei; Gekkota-the leopard gecko Eublepharis macularius and the mourning gecko Lepidodactylus lugubris; and Lacertidae-the sand lizard Lacerta agilis. Three-dimensional reconstructions were created from thick serial sections and high-resolution semithin sections. Pancreatic islet cells in lizards originate from ductal epithelium. Early in development, precursor cells leave the duct walls to form buds that give rise to primary islets, a process evolutionarily conserved across vertebrates. Subsequent growth involves both the fusion of islet buds and the fission of larger agglomerates. Analyzed species differ in islet distribution: The brown anole islet remains restricted to the splenic lobe, whereas the sand lizard, leopard gecko, and mourning gecko also form islets in remaining regions. In studied gekkotans, small- and medium-sized islets tended to be concentrated in close proximity to the spleen. Medium-sized islets dominate the splenic lobe in the sand lizard. Interestingly, we observed a varanid-like condition in the brown anole, characterized by the formation of a single large islet within the splenic lobe, accompanied by a concurrent reduction in islet size throughout the remaining pancreatic regions. This pattern may reflect a broader trend within Toxicofera, a clade identified through molecular studies, toward splenic lobe islet enlargement and a reduction in the size of the islets in the remaining parts of the pancreas. While the phylogenetic position may influence these patterns, our findings suggest that the spatial relationship between the spleen and pancreas, particularly the formation of large islets near the spleen, could play a more direct, possibly inductive, role in islet formation. Further detailed studies, particularly focusing on representatives of Iguania and Anguimorpha, are essential to test this hypothesis.