Abstract
The Hippo signaling pathway is a vital regulator of pancreatic development and homeostasis, directing cell fate decisions, morphogenesis, and adult pancreatic cellular plasticity. Through loss-of-function research, Hippo signaling has been found to play key roles in maintaining the proper balance between progenitor cell renewal, proliferation, and differentiation in pancreatic organogenesis. Other studies suggest that overactivation of YAP, a downstream effector of the pathway, promotes ductal cell development and suppresses endocrine cell fate specification via repression of Ngn3. After birth, disruptions in Hippo signaling have been found to lead to de-differentiation of acinar cells and pancreatitis-like phenotype. Further, Hippo signaling directs pancreatic morphogenesis by ensuring proper cell polarization and branching. Despite these findings, the mechanisms through which Hippo governs cell differentiation and pancreatic architecture are yet to be fully understood. Here, we review recent studies of Hippo functions in pancreatic development, including its crosstalk with NOTCH, WNT/β-catenin, and PI3K/Akt/mTOR signaling pathways.
Highlights
Hippo signaling plays an important role in regulating cell proliferation and apoptosis; it is thought to be a central regulator of organ size and tissue homeostasis
The Hippo signaling pathway is an essential regulator of pancreatic development, directing cell differentiation and organ morphogenesis
Great progress has been made toward uncovering the mechanisms through which Hippo governs pancreatic development, there are still several components of the pathway that warrant further study
Summary
Yifan Wu1,2, Pauline Aegerter, Michael Nipper, Logan Ramjit, Jun Liu and Pei Wang1*. The Hippo signaling pathway is a vital regulator of pancreatic development and homeostasis, directing cell fate decisions, morphogenesis, and adult pancreatic cellular plasticity. Through loss-of-function research, Hippo signaling has been found to play key roles in maintaining the proper balance between progenitor cell renewal, proliferation, and differentiation in pancreatic organogenesis. Other studies suggest that overactivation of YAP, a downstream effector of the pathway, promotes ductal cell development and suppresses endocrine cell fate specification via repression of Ngn. Hippo signaling directs pancreatic morphogenesis by ensuring proper cell polarization and branching. Despite these findings, the mechanisms through which Hippo governs cell differentiation and pancreatic architecture are yet to be fully understood. We review recent studies of Hippo functions in pancreatic development, including its crosstalk with NOTCH, WNT/β-catenin, and PI3K/Akt/mTOR signaling pathways
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