β1 integrin is a crucial regulator of pancreatic β-cell expansion

• DOI: 10.1242/dev.098533
• Publication Date: 2013-07-18T01:47:53Z
• Authors: Giuseppe R. Diaferia; Antonio J. Jimene...; Prerana Ranjitkar; Wendy Yang; Gary Hardiman; Christopher J. Rh...; Laura Crisa; Vincenzo Cirulli
• Keywords: Enteroendocrine cell

Development of the endocrine compartment pancreas, as represented by islets Langerhans, occurs through a series highly regulated events encompassing branching pancreatic epithelium, delamination and differentiation islet progenitors from ductal domains, followed expansion three-dimensional organization into clusters. Cellular interactions with extracellular matrix (ECM) mediated receptors integrin family are postulated to regulate key functions in these processes. Yet, specific developing pancreas remain unknown. Here, we show that ablation β1 gene β-cells reduces their ability expand during embryonic life, first week postnatal thereafter. Mice lacking insulin-producing cells exhibit dramatic reduction number only ∼18% wild-type levels. Despite significant β-cell mass, mutant mice not diabetic. A thorough phenotypic analysis revealed normal expression repertoire markers, architectural within clusters, ultrastructure. Global this ECM receptor inhibits genes regulating cell cycle progression. Collectively, our results demonstrate function crucial positive regulators expansion.