An ultrastructural analysis of the developing embryonic pancreas

Pictet, Raymond; Clark, William R.; Williams, Robert H.; Rutter, William J.

doi:10.1016/0012-1606(72)90083-8

Cited by 489 publications

(325 citation statements)

References 25 publications

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“…The following period beginning at E13, known as the second transition, is characterized by the rapid expansion of endocrine and exocrine precursor cells from the duct epithelium and their spatial and temporal differentiation into the exocrine and endocrine lineages (Pictet et al, 1972;Przybyla et al, 1979;Slack, 1995). During the second transition, the pancreas is extensively remodeled by the combination of: 1) proliferation and branching morphogenesis of the primitive ductal epithelium, 2) differentiation of exocrine cells into acini from ductal precursors, and 3) the formation and delamination of endocrine cells, consisting of the alpha, beta, delta, and PP cells (that produce the hormones, glucagon, insulin, somatostatin, and pancreatic polypeptide, respectively) (Kim and MacDonald, 2002).…”

Section: Resultsmentioning

confidence: 99%

Snail2, a mediator of epithelial-mesenchymal transitions, expressed in progenitor cells of the developing endocrine pancreas

Rukstalis

Habener

2007

Gene Expression Patterns

110

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The mammalian pancreas develops by the expansion and morphogenesis of the epithelial cells of the foregut endoderm via the sequential activation of transcription factors that direct differentiation into the various pancreatic lineages. Implicit in this growth and differentiation are the temporal and spatial processes of cell migration and three-dimensional organization, which cooperate to form a properly functioning organ. In many organ systems, such as the kidney, heart, and neural crest derivatives, migration and tissue morphogenesis is accomplished by the transient conversion of stationary epithelial cells to migratory mesenchymal-like cells in a process known as epithelial-mesenchymal transition (EMT). We report the identification of the expression of the transcription factor Snail2/ Slug, a known inducer of EMT and cell movement, in both the endocrine and exocrine cells of the developing mouse pancreas. Snail2 is expressed in Neurogenin3-positive endocrine progenitor cells, and expression is maintained during endocrine cell differentiation where it becomes increasingly restricted to the insulin-producing beta cells and somatostatin-producing delta cells. In the adult pancreas, the expression of Snail2 is maintained at low but detectable levels in all beta cells, indicating a latent role for Snail2 in the mature islet. These findings of Snail2 expression during endocrine pancreas development are relevant to the recent evidence demonstrating the involvement of EMT in the expansion of human islet tissue in vitro. EMT-like events appear to be involved in the development of the mammalian pancreas in vivo.

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Section: Resultsmentioning

confidence: 99%

Snail2, a mediator of epithelial-mesenchymal transitions, expressed in progenitor cells of the developing endocrine pancreas

Rukstalis

Habener

2007

Gene Expression Patterns

110

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“…In the rodent there are two phases of islet cell expansion in utero. The first occurring at mouse embryonic day 9 consists almost entirely of glucagon-positive cells (Pictet et al, 1972). The second wave of expansion of endocrine cells is noted at day 15 (Han et al, 1986).…”

Section: Effects Of Glp-1r Activation During Pancreatic Development Amentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

576

465

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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“…It is believed that the majority of endocrine cells that contribute to the mature islets present at the end of gestation are generated during these stages. Proacini also begin differentiation from the numerous distal tips of the pancreatic epithelium, and move into synthesizing high levels of acinar digestive enzymes in addition to CpaI, such as amylase, elastase, and trypsinogen (Pictet et al, 1972). After about E14.5, acinar cells are mainly generated by the duplication of existing acinar cells, and endocrine progenitor birth in the trunk domain ends by the beginning of postnatal life (Zhou et al, 2007;Solar et al, 2009).…”

Section: The Secondary Transition: Onset Of Islet Duct and Acinar DImentioning

confidence: 99%

“…The main events in this transition include active proliferation of pancreatic progenitors to generate a stratified epithelium, followed by formation of multiple microlumens and their subsequent coalescence, which serves as the precursor for turning the entire pancreatic primordium, via a plexus intermediate, into a growing epithelial arbor. The first differentiated endocrine cells, mainly glucagon-producing a-cells, begin to appear in the dorsal bud at this phase of development, in a cluster-budding process, rather than by individual delamination of epithelial cells (Pictet et al, 1972;Herrera, 2000;Kesavan et al, 2009;Villasenor et al, 2010). At E11.5, the gut tube begins to undergo its first coiling movements, a rotation that brings the dorsal and ventral buds into proximity for their future conjoining into a single organ.…”

mentioning

confidence: 99%

Pancreas organogenesis: From bud to plexus to gland

Pan

Wright

2011

Developmental Dynamics

525

594

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Pancreas oganogenesis comprises a coordinated and highly complex interplay of signaling events and transcriptional networks that guide a step-wise process of organ development from early bud specification all the way to the final mature organ state. Extensive research on pancreas development over the last few years, largely driven by a translational potential for pancreatic diseases (diabetes, pancreatic cancer, and so on), is markedly advancing our knowledge of these processes. It is a tenable goal that we will one day have a clear, complete picture of the transcriptional and signaling codes that control the entire organogenetic process, allowing us to apply this knowledge in a therapeutic context, by generating replacement cells in vitro, or perhaps one day to the whole organ in vivo. This review summarizes findings in the past 5 years that we feel are amongst the most significant in contributing to the deeper understanding of pancreas development. Rather than try to cover all aspects comprehensively, we have chosen to highlight interesting new concepts, and to discuss provocatively some of the more controversial findings or proposals. At the end of the review, we include a perspective section on how the whole pancreas differentiation process might be able to be unwound in a regulated fashion, or redirected, and suggest linkages to the possible reprogramming of other pancreatic cell-types in vivo, and to the optimization of the forward-directed-differentiation of human embryonic stem cells (hESC), or induced pluripotential cells (iPSC), towards mature b-cells. Developmental Dynamics 240:530-565,

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An ultrastructural analysis of the developing embryonic pancreas

Cited by 489 publications

References 25 publications

Snail2, a mediator of epithelial-mesenchymal transitions, expressed in progenitor cells of the developing endocrine pancreas

Snail2, a mediator of epithelial-mesenchymal transitions, expressed in progenitor cells of the developing endocrine pancreas

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Pancreas organogenesis: From bud to plexus to gland

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