Transient Impairment of Islet Architectural Development in Pancreas-Specific Bmpr1a-Deleted Prenatal Mice Involves Reduced Expression of E-Cadherin

Stem Cells Dev. 2017 Dec 1;26(23):1706-1714. doi: 10.1089/scd.2017.0040. Epub 2017 Oct 30.

Abstract

Bone morphogenetic protein (BMP) signaling plays critical roles on the development of a large array of embryonic organs and promotes the in vitro formation of pancreatic cystoid colonies containing insulin-producing cells. However, this signaling and its underlying mechanism on in vivo development of prenatal pancreas have not been clearly understood. To address these questions, we analyzed, with a variety of techniques, the prenatal mouse pancreas after Pdx1 (the pancreas and duodenum homeobox factor 1 gene)-driving deletion of the BMP receptor type 1a gene (Bmpr1a). In this study, we report that the Pdx1-driving deletion of Bmpr1a transiently disrupted only the assembly of architectural structure of prenatal islets. The differentiation of endocrine lineage cells and the development of pancreatic acinar tissue were comparable between Bmpr1a-deleted fetuses and -undeleted Controls throughout the period examined. Molecular studies revealed that among many proteins surveyed, the key cell-cell interaction molecule E-cadherin (E-cad) only was expressed significantly less at both messenger RNA (mRNA) and protein levels in Bmpr1a-deleted than Control fetal endocrine cells. We thus conclude that BMP signaling transiently regulates the expression of E-cad and the establishment of prenatal islet architecture.

Keywords: Bmpr1a; E-cadherin; architectural development; islets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein Receptors, Type I / genetics*
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Differentiation
  • Cells, Cultured
  • Gene Deletion
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / embryology
  • Islets of Langerhans / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction

Substances

  • Cadherins
  • Bmpr1a protein, mouse
  • Bone Morphogenetic Protein Receptors, Type I