Exploring the Molecular Crosstalk between Pancreatic Bud and Mesenchyme in Embryogenesis: Novel Signals Involved

• DOI: 10.3390/ijms20194900
• Publication Date: 2019-10-03T07:41:27Z
• Authors: Ilaria Guerriero; Maria Teresa De A...; Fulvio D’Angelo; Rita Leveque; Eleonora Savignano; Luca Roberto; Valeria Lucci; Pellegrino Mazzone; Simona Laurino; Giovanni Storto; Anna Nardelli; Alessandro Sgambato; Michele Ceccarelli; Mario De Felice; Elena Amendola; Geppino Falco
• Keywords: 0301 basic medicine; Gene Expression Profiling; Organogenesis; pancreatic disorders; Pancreas;omics; Computational Biology; Embryonic Development; Gene Expression Regulation, Developmental; progenitor cells; [object Object]; embryonic stem cells; bud; Article; omics; 3. Good health; Mesoderm; pancreatic stem cells; Mice; 03 medical and health sciences; laser microdissection; Animals; Pancreatic organogenesis; Pancreas; mesenchymal stem cell; Signal Transduction

Pancreatic organogenesis is a multistep process that requires the cooperation of several signaling pathways. In this context, the role of pancreatic mesenchyme is important to define the epithelium development; nevertheless, the precise space–temporal signaling activation still needs to be clarified. This study reports a dissection of the pancreatic embryogenesis, highlighting the molecular network surrounding the epithelium–mesenchyme interaction. To investigate this crosstalk, pancreatic epithelium and surrounding mesenchyme, at embryonic day 10.5, were collected through laser capture microdissection (LCM) and characterized based on their global gene expression. We performed a bioinformatic analysis to hypothesize crosstalk interactions, validating the most promising genes and verifying the precise localization of their expression in the compartments, by RNA in situ hybridization (ISH). Our analyses pointed out also the c-Met gene, a very well-known factor involved in stimulating motility, morphogenesis, and organ regeneration. We also highlighted the potential crosstalk between Versican (Vcan) and Syndecan4 (Sdc4) since these genes are involved in pancreatic tissue repair, strengthening the concept that the same signaling pathways required during pancreatic embryogenesis are also involved in tissue repair. This finding leads to novel strategies for obtaining functional pancreatic stem cells for cell replacement therapies.