Talk:Gastrointestinal Tract - Pancreas Development

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Cite this page: Hill, M.A. (2021, November 30) Embryology Gastrointestinal Tract - Pancreas Development. Retrieved from


Identification and fate mapping of the pancreatic mesenchyme

Dev Biol. 2018 Mar 1;435(1):15-25. doi: 10.1016/j.ydbio.2018.01.003. Epub 2018 Jan 9.

Angelo JR1, Tremblay KD2.


The murine pancreas buds from the ventral embryonic endoderm at approximately 8.75 dpc and a second pancreas bud emerges from the dorsal endoderm by 9.0 dpc. Although it is clear that secreted signals from adjacent mesoderm-derived sources are required for both the appropriate emergence and further refinement of the pancreatic endoderm, neither the exact signals nor the requisite tissue sources have been defined in mammalian systems. Herein we use DiI fate mapping of cultured murine embryos to identify the embryonic sources of both the early inductive and later condensed pancreatic mesenchyme. Despite being capable of supporting pancreas induction from dorsal endoderm in co-culture experiments, we find that in the context of the developing embryo, the dorsal aortae as well as the paraxial, intermediate, and lateral mesoderm derivatives only transiently associate with the dorsal pancreas bud, producing descendants that are decidedly anterior to the pancreas bud. Unlike these other mesoderm derivatives, the axial (notochord) descendants maintain association with the dorsal pre-pancreatic endoderm and early pancreas bud. This fate mapping data points to the notochord as the likely inductive source in vivo while also revealing dynamic morphogenetic movements displayed by individual mesodermal subtypes. Because none of the mesoderm examined above produced the pancreatic mesenchyme that condenses around the induced bud to support exocrine and endocrine differentiation, we also sought to identify the mesodermal origins of this mesenchyme. We identify a portion of the coelomic mesoderm that contributes to the condensed pancreatic mesenchyme. In conclusion, we identify a portion of the notochord as a likely source of the signals required to induce and maintain the early dorsal pancreas bud, demonstrate that the coelomic mesothelium contributes to the dorsal and ventral pancreatic mesenchyme, and provide insight into the dynamic morphological rearrangements of mesoderm-derived tissues during early organogenesis stages of mammalian development.

Copyright © 2018 Elsevier Inc. All rights reserved.

PMID: 29329912 PMCID: PMC5937278 DOI: 10.1016/j.ydbio.2018.01.003


Modulation of pancreatic exocrine and endocrine secretion

Curr Opin Gastroenterol. 2013 Sep;29(5):517-22. doi: 10.1097/MOG.0b013e3283639326.

Chandra R1, Liddle RA. Author information


PURPOSE OF REVIEW: Recent advances in the regulation of pancreatic secretion by secretagogues, modulatory proteins and neural pathways are discussed. RECENT FINDINGS: Downstream events involved in secretagogue stimulation of pancreatic secretion have been elucidated through characterization of the Src kinase pathway. An additional mechanism regulating vagus nerve effects on the pancreas involves Group II and III metabotropic glutamate receptors that are located presynaptically on certain vagal pancreas-projecting neurons. Hypothalamic neurons perceive glucose and regulate insulin release by direct communication with islets, and activation of proopiomelanocortin neurons by leptin enhances insulin secretion and modulates glucose but not energy homeostasis. Ghrelin and somatostatin mediate glucose-stimulated insulin secretion by differential receptor signaling that is dependent on the amount of ghrelin and state of receptor heterodimerization. Endoplasmic reticulum (ER) stress and loss-of-function mutations of a key ER stress protein are associated with disruption of membrane translocation and reduction in insulin secretion. The importance of hormones, neuropeptides, amino acids, cytokines and regulatory proteins in pancreatic secretion and the pathophysiology of type 2 diabetes are also discussed. SUMMARY: The biomolecular pathways regulating pancreatic secretions are still not fully understood. New secretagogues and mechanisms continue to be identified and this information will aid in drug discovery and development of new and improved therapy for pancreatic disorders.

PMID 23817137


Pancreas organogenesis: from bud to plexus to gland

Dev Dyn. 2011 Mar;240(3):530-65. doi: 10.1002/dvdy.22584. Pan FC, Wright C.


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 β-cells. Copyright © 2011 Wiley-Liss, Inc.

PMID 21337462

Pancreatic ductal cells in development, regeneration, and neoplasia

J Clin Invest. 2011 Dec;121(12):4572-8. doi: 10.1172/JCI57131. Epub 2011 Dec 1.

Reichert M, Rustgi AK. Source Division of Gastroenterology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.


The pancreas is a complex organ comprised of three critical cell lineages: islet (endocrine), acinar, and ductal. This review will focus upon recent insights and advances in the biology of pancreatic ductal cells. In particular, emphasis will be placed upon the regulation of ductal cells by specific transcriptional factors during development as well as the underpinnings of acinar-ductal metaplasia as an important adaptive response during injury and regeneration. We also address the potential contributions of ductal cells to neoplastic transformation, specifically in pancreatic ductal adenocarcinoma.

PMID 22133881


Direct measurement of pancreatic enzymes: a comparison of secretagogues

Dig Dis Sci. 2002 Oct;47(10):2211-6.

Pfefferkorn MD1, Fitzgerald JF, Croffie JM, Gupta SK, Caffrey HM. Author information


Direct measurement of pancreatic enzymes is the gold standard in the evaluation of exocrine pancreatic function. The purpose of our study was to evaluate the use of cholecystokinin as a single-agent secretagogue for pancreatic drainage studies. Twenty pediatric patients received cholecystokinin (group 1) and 40 patients received either secretin plus placebo (group 2) or secretin plus cholecystokinin (group 3). Duodenal fluid was collected for measurement of lipase, amylase, trypsin, chymotrypsin. The mean lipase and amylase activities were higher in group 3 and the mean trypsin and chymotrypsin activities were higher in group 1, but none of these observations were statistically significant. Group 3 had more patients with all four enzymes being normal (75%) compared to groups 1 (60%) and 2 (50%) (P = 0.262). Patients in all three groups had at least one normal enzyme. Cholecystokinin is useful as a single agent for direct pancreatic enzyme measurements in the absence of commercially available secretin. PMID 12395893


Development of functional responses in human exocrine pancreas

Pediatrics. 1980 Oct;66(4):556-60.

Lebenthal E, Lee PC.


The ability of newborns to digest proteins, fats, and carbohydrates depends, to a large extent, on their level of exocrine pancreatic function. Building on the limited published data, we studied pancreatic enzyme activities in the duodenal fluid and the response of the exocrine pancreas to secretogogues in 15 premature and full-term infants at birth and at 30 days of age. We compared these findings to those obtained from identical studies of 17 children age 2 years and above. In addition, we measured the pancreatic exopeptidase, carboxypeptidase B, in relation to other pancreatic enzymes. The duodenal fluid of newborns and infants contained no amylase and negligible lipase. Carboxypeptidase B levels were also low compared to those in the older children. In contrast, chymotrypsin activity in infants was about 50% to 60% of level found in the older children. Trypsin activity, the highest of all the enzymes measured, was about the same in both newborns and older children, with a transient increase at 30 days. Administration of pancreozymin had no effect on pancreatic enzymes in the duodenal fluid of newborns and a slight effect on 1-month-old infants. But by age 2 years, a full response of the pancreas to pancreozymin was evident. In infants and newborns, responses to secretin were poor. Thus, the secretory response of the human pancreas to secretogogues, absent or minimal at birth, is acquired during the postnatal period.

PMID 6159567


Differential expression of salivary (Amy1) and pancreatic (Amy2) human amylase loci in prenatal and postnatal development

J Med Genet. 1976 Apr;13(2):96-102.

Tye JG, Karn RC, Merritt AD.


The age-dependent development of alpha-amylase expression in utero and during the first two years of life is reported. Separation of salivary and pancreatic amylase isozymes in a discontinuous buffered sheet polyacrylamide electrophoretic system, with subsequent densitometry, provides a reliable semiquantitative method of estimating the proportions of salivary and pancreatic amylases in urine and amniotic fluid samples. In the newborn the predominant amylase isozymes seen in the urine are of salivary origin. As the child ages the level of amylase in the urine rises and an increase in the proportion of pancreatic amylase isozymes occurs. Amniotic fluids of late first and early second trimester pregnancies contain salivary isozymes. None of the amniotic fluid samples examined has pancreatic amylase isozymes. These data reflect a differential development of the expression of the two amylase approaches adult levels by 16 months of age. Conversely, the salivary (Amy1) locus is expressed as early as 18 weeks of gestation and remains relatively constant with but a small increase in salivary amylase (units/ml) activity during early development, as the total amylase activity approaches adult values. PMID: 933119 PMCID: PMC1013368