Cutting the Edge of β-Cells - WNT Pathway Thrives Lineage Segregation in Pancreatic Organogenesis

Abstract

Lately Revealed by Genome-wide association studies (GWAS) the association of TCF7L2 and Type 2 Diabetes (T2D) which implicates underlying mechanism of this Wingless (WNT) pathway effector gene in pancreatic s-cell development. Also, further research linking TCF7L2 to T2D and impaired s-cell mass accomplished by insulin secretory malfunction, shed light on the regulatory function of this particular canonical WNT pathway member. Thus, highlighting the fact that indeed Dishevelled (DEL) regulates as a scaffold protein in canonical and non-canonical WNT regulatory pathway components. Fairly is understood in the process of canonical and non-canonical WNT signaling, except that DEL acts through transmembrane domains of co-/receptors as Frizzled (FZ) and Low-density lipoprotein receptor-related protein 5 (LRP5). Well described in the context of regulatory mechanism is the canonical WNT signaling pathway, resulting in stabilization/activation of functional s-catenin in line with accumulation in a multi-protein complex at the specifically located membrane surface. Contrary the absence of WNT signaling components determines the destabilization/degradation of s-catenin. Thus, either supporting junctional complexes of neighboring cells for the formation of the epithelial cell sheet or by degradation initiate cell differentiation/ segregation within the epithelial sheet. Also, the non-canonical WNT signaling pathway suggests to be part of the intracellular trafficking vesicular network and thereby regulate cytoskeletal control and polarization, respective migration of a specific subset of cells. Mainly, these processes are undertaken by non-canonical pathway divisions as the Planar Cell Polarity (PCP) and calcium (Ca2+) pathway. We will focus in this review on common highlights of WNT pathway components in pancreatic organogenesis in the secondary transition as the different lineages of the pancreas segregate. Also, further dissecting the various WNT ligands and core components at this specific stage in the mesenchyme and epithelium will enable putative mechanism regarding tissue remodeling and tubulogenesis in line with lineage differentiation of the pancreatic gland.