Pancreas Organogenesis: From Lineage Determination to Morphogenesis

Abstract

The pancreas is an essential organ for proper nutrient metabolism and has both endocrine and exocrine function. In the past two decades, knowledge of how the pancreas develops during embryogenesis has significantly increased, largely from developmental studies in model organisms. Specifically, the molecular basis of pancreatic lineage decisions and cell differentiation is well studied. Still not well understood are the mechanisms governing three-dimensional morphogenesis of the organ. Strategies to derive transplantable β-cells in vitro for diabetes treatment have benefited from the accumulated knowledge of pancreas development. In this review, we provide an overview of the current understanding of pancreatic lineage determination and organogenesis, and we examine future implications of these findings for treatment of diabetes mellitus through cell replacement.

Virgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets

“…Based on the totality of these observations, we propose that the islet periphery contains a specialized 'neogenic niche'; a specific micro-environment where the necessary cues and conditions to facilitate islet cell plasticity are met. The differentiation of pancreatic beta cells during embryonic development is driven by spatio-temporal gradients that determine the formation of endocrine progenitors at the trunk of the budding ducts followed by their delamination from the ductal epithelia to eventually cluster into islets (Shih et al, 2013).…”

“…Both Ucn3 low and Ucn3 negative beta cells localized peripherally, just internally from alpha cells in the mouse islet ( Figure 1J). When broken down by age, immature and mature beta cell populations in the first postnatal week distributed in proximity, but segregated as adult architecture is established (Shih et al, 2013) ( Figure S1). …”

Agenesis of the dorsal pancreas: systematic review of a clinical challenge

“…DPA is a rare malformation caused by the absence of the dorsal pancreatic bud of the endoderm (1,35,36). The entity was first described by Heiberg in 1911 (3) The clinical manifestations of DPA reflect the abnormalities in the embryogenesis of the dorsal pancreas.…”

“…The left ventral bud regresses whilst the right ventral bud migrates posteriorly together with the rotation of the gut at 6-7 weeks of gestation (G 6-7w) and fuses with the dorsal bud. With the fusion of both buds, morphogenesis and differentiation begin in the acinar, ductal and endocrine cells (1,35,37,38).…”

“…Dorsal pancreatic agenesis (DPA) is a very rare malformation which consists of the absence of the neck, body and tail of the pancreas derived from the bud of the dorsal endoderm (1,2). This anomaly was first described in 1911, and 53 cases were reported up to 2008 (3,4).…”