Pancreas development in fishes, amphibians, reptiles birds and mammals which factors involve in development of pancreas. Different cells involved in pancreas development.
2. Overview
• 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, lobulated 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. DevelopmentofPancreas
The pancreas develops from the two buds
Ventral bud: Arises from the hepatic
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 10th 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. Developmentof pancreaticducts
• 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.
1. Acinar development progress through three stages predifferetiated
protodifferentiated and differentiated stages.
2. 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. Signallingpathways:Pancreas
• The signaling pathways underlying the development process include the
Hedgehog system, the homeobox gene :Pdx1 and Notch signaling [1,2].
• Inhibition of Hedgehog signaling leads to ectopic budding of pancreatic
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.)
Neurogenin-3 ,a protein is expressed in endocrine progenitor cells and
is required for endocrine cell development in the pancreas.
10. PancreaticAgenesis and Hypoplasiaof the Dorsal
Pancreas:congenitalshortpancreas
• 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: DevelopmentofPancreas
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.
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Anatomy: A Clinical Problem-Solving Approach. 11th ed. London,
UK: Williams and Wilkins; 1989.
4. 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).
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.
6. 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