Development of pancreas from pices to mammals.

Pancreas development in fishes, amphibians, reptiles birds and mammals which factors involve in development of pancreas. Different cells involved in pancreas development.

1. Development of the Pancreas Development of pancreas Nizad sultana Department of Zoology UOG Development of pancreas

2. O v e r v i e w The pancreas , named from the Greek words pan (all) and kreas (flesh), is a 12-15–cm long J-shaped (like a hockey stick), soft, lobulate d organ. The adult gland weighs between 70 and 110 g.

3. Histology Light stained clusters of cells are called islets of Langerhans these produce hormones that underlie the endocrine function of pancreases. Dark stained cells form acini that are connected to ducts. Acinar cells belong to exocrine pancreas and secrete digestive enzymes into gut via system of ducts. Four main types of cell exist in islets. Alpha cell secrete glucagon Beta cell secrete insulin Delta cells secrete somatostatin PP cells or gamma cells secrete pancreatic polypeptide .

4. Development of Pancreas The pancreas develops from the two buds V en t r a l bu d : Ar i s e s f r o m the h e p a t i c diverticulum and gives the lower part of the head and uncinated process. Dorsal bud : Arises from the dorsal aspect of the duodenum and gives the upper part of the head neck , body & tail. 4 to 7 weeks : reference Sleisenger 10 th ed.

5. Rotation and Fusion Definitive pancreas results from rotation of ventral bud and fusion of two buds during development duodenum rotates to right ventral bud rotates with it. Upon reaching its destination the ventral pancreatic bud is below dorsal bud and eventually fuses with it. Both buds fuse to form main pancreatic duct. Usually ducts of dorsal bud regresses leaving main duct.

6. Development of pancreatic ducts The main pancreatic duct(duct of wirsung) : from the duct of ventral pancreas (proximally) and from distal part of the duct of dorsal pancreas (distally). The accessory pancreatic duct(duct of Santorini) : from the proximal part of the duct of the dorsal pancreas. Development of pancreatic acini and islets Side branches extend from the ducts to the surrounding mesoderm. Some of them become canalized pancreatic acini. Others separate & not canalized Islets of Langerhans. The pancreatic connective tissue stroma and interlobar septa: from the splanchnic mesoderm.

7. Cellular development Pancreatic progenitor cells also known as precursor cells differentiate into functional pancreatic cells exocrine acinar cells endocrine islets cell and ductal cells. There are different molecules that induce differentiation follistatin fibroblast growth factors and Notch receptor system . Acinar development progress through three stages predifferetiated protodifferentiated and differentiated stages. Endocrine islets form under the influence of ISL1,neurogenin 3 but in absence of Notch receptor signaling.

8. Pancreatic islets formation Endocrine precursor cell under influence of Pax gene form alpha and gamma cells. while under the influence of Pax 6 form beta and delta cells 3.The pancreatic islets form as the endocrine cells migrate from duct system to form small clusters around capillaries. This occurs during 3 month of development then insulin and glucagon can be detected in fetal circulation by fourth and fifth month of development.

9. Signalling pathways : Pancreas Th e signal i n g p a t h w a y s u n derly i n g the de v elopm e n t p r oc e s s i nc lu d e t h e Hedgehog system, the homeobox gene :Pdx1 and Notch signaling [1,2]. Inhibiti o n o f He d ge h o g sig n alin g l eads t o ec t opi c buddin g o f panc r eatic structures in the stomach and the duodenum . Pdx1 expression in the duodenum during development marks the location of pancreatic bud development . Notch signaling inhibits endocrine cell differentiation and promotes exocrine cell differentiation . ( Inhibition of Notch signaling results in marked endocrine cell expansion with blockade of exocrine cell development.) Neur o g e ni n - 3 , a pro t ein is e x p r ess e d in e n d oc r ine p r oge ni t o r c ells an d is required for endocrine cell development in the pancreas.

10. Pancreatic Agenesis and Hypoplasia of the Dorsal Pancreas: congenital short pancreas Total agenesis of the pancreas is extremely rare and is incompatible with life. Hypoplasia (partial agenesis) results from the absence of the ventral or dorsal pancreatic anlage. Mutations in PDX1 have been reported in humans with pancreatic agenesis.(1) Patients with dorsal pancreatic agenesis have an increased risk of DM because most of the islet cells are located in the distal pancreas (2).

11. Summary: Development of Pancreas Two outpouchings of the endodermal lining of the duodenum Dorsal Bud lower part of the head uncinated process upper part of the head neck body & tail Week 7 to 20 - pancreatic hormones secretion increases, small amount maternal insulin Week 10 - glucagon (alpha) differentiate first, somatostatin (delta), insulin (beta) cells differentiate, insulin secretion begins Week 15 - glucagon detectable in fetal plasma Ventral Bud

12. Exocrine endocrine functions The pancreas exocrine function begins after birth, while the endocrine function (hormone release) can be measured from 10 to 15 weeks onward. At this stage, it is not clear what the exact roles of these hormones are in regulating fetal growth. Pancreas adult Functions - exocrine (amylase, alpha-fetoprotein), 99% by volume; endocrine (pancreatic islets) 1% by volume about 1 million islets Exocrine function - begins after birth Endocrine function - from 10 to 15 weeks onward hormone release exact roles of hormones in regulating fetal growth?

13. Pancreas in vertebrates Pancreatic tissues present in all vertebrates but its precise form and arrangement varies. There may be upto three separate pancreases two of which arises from ventral bud and other from dorsal. In most species including humans these fuse in adult but there are many exceptions.

14. In birds Endocrine pancreas contain 3 islets type. However of islets of Langerhans is less define than mammals. Avian pancreas is comprises of A islets containing A1 and A2 cell types and B islets containing A2 and B cell function of A2 and B cell is secretion of glucagon and insulin respectively while that of A1 is uncertain. Avian pancreas contains small amount of insulin has poor insulinogenic potential. Avian pancreas contain 5/10 times more glucagon than mammals.

15. Reptiles Pancreas of snakes is simpler pyramid shape attach to first portion of duodenum in some snakes there is limb of pancreas that runs forward to spleen in others limb is interrupted or either absent. Pancreas of lizard is more complex than snake and is trilobed one portion runs along bile duct towards gall bladder one portion runs to small intestine and a thin limb runs towards spleen. In alligator mississipipiensis ventral portion of pancreas is between the limbs of ventral duodenal loop.

16. Comparison Most reptiles pancreas lacks a sharp demarcation that is present in mammals. Islets of lizard is more centrally located than in snake which is more peripheral. Turtle islet is smaller and more diffusely distributed while crocodilian islets is highly branched. Alpha and beta cells

17. Amphibians The pancreas contains two distinct populations of cells exocrine cells which secretes enzymes into digestive tract and endocrine cells which secrete hormones into bloodstream. Pancreas arises from endoderm as dorsal and ventral bud that fuses together to form single organ. Mammals birds reptiles and amphibians have similar morphology and mode of development with little deviations but differs in some fishes.

18. Fishes In some fishes islets cell segregate as Brockmann bodies. Pancreas in N.kaiser Pancreas in Huso Huso has thick capsule. Most primitive arrangement appears in lampreys and lungfish pancreatic tissue is found as number of discrete nodules within wall of gut itself exocrine portion little different from other glandular structure of intestine. Pancreases is absent in cyclostomata a class of aganatha.

19. Agur AMR, Lee MJ, Grant JCB. Grant’s Atlas of Anatomy. 10th ed. London, UK: Lippincott Williams and Wilkins; 1999. Romanes GJ. Cunningham's Manual of Practical Anatomy. 15th ed. New York, NY: Oxford Medical Publications, Oxford University Press; 1986. Vol II: Thorax and Abdomen. Grant JCB, Basmajian JV, Slonecker CE. Grant's Method of Anatomy: A Clinical Problem-Solving Approach. 11th ed. London, UK: Williams and Wilkins; 1989. Habener, J.F., Kemp, D.M., and, M.K. Thomas, Minireview: transcriptional regulation in pancreatic development. Endocrinology, 2005. 146(3): pp. 1025 – 34. Kim, S.K., and MacDonald, R.J., Signaling and transcriptional control of pancreatic organogenesis. Curr Opin Genet Dev, 2002. 12(5). Stoffers DA, Zinkin NT, Stanojevic V, et al. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nat Genet 1997; 15:106-10. Lång K, Lasson A, Müller MF, Thorlacius H, Toth E, Olsson R. Dorsal agenesis of the pancreas - a rare cause of abdominal pain and insulin-dependent diabetes. Acta Radiol. 2012;53:2-4

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