Development of liver and - PowerPoint Presentation

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Development of liver and pancreas

Semmelweis

University

,

Department of

Anatomy

,

Histology

and

Embryology

Dr. Kocsis Katalin

2020.04.23.

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Development of the foregut

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upper

limb

atlas

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Hox

gene expression boundaries in the endoderm and mesoderm during early chick gut development. Specific combinations of homeobox gene expression can be mapped to specific regions of the gastrointestinal tract, with some combinations demarcating the position of sphincters and organs. The regional expression patterns of mouse homologs are similar.

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Figure 14-5 Signals and transcription factors important in establishing regional differences in the early developing gastrointestinal tract. The top drawing represents an early mammalian embryo shortly after the initiation of embryonic folding, with areas enlarged below showing some of the signaling events involved in liver, pancreas, and hindgut specification. After initiation of cranial body folding, the endoderm of the ventral foregut is situated adjacent to the caudal cardiogenic mesoderm and septum transversum. Tissue-tissue interactions between the cardiogenic mesoderm and the endoderm, mediated by

Fgf

and

Bmp

signals, induce hepatocytic markers within the endoderm (e.g.,

Albumin

and

Alpha fetoprotein

) while suppressing pancreatic development by upregulating

Shh

expression. The homeoprotein pancreatic/duodenal marker,

Pdx1, promotes pancreatic development. However, in the presence of Shh, pancreatic development is repressed. Much of the endoderm expresses Shh, but it is repressed by notochordal release of Fgfs and Activin B in the future pancreatic region. Shh expression within the hindgut endoderm induces Bmp4 and Hoxd13 expression within the caudal mesoderm. Shh/Bmp4 are only capable of inducing Hoxd13 expression in the caudal gut, possibly due to the caudal restriction of Cdx2 expression established during gastrulation. Hoxd13 instills a caudal identity to the hindgut. Alb, Albumin, Afp, Alpha fetoprotein; Ipf1, insulin promoter factor 1.

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26 D

20 D

24 D

26 D

ductus omphalo-entericus

aortic arch

foregut

aorta

a. vitellina

hindgut

a. umbi-licalis

entoderm

yolk sac

midgut

allantois

foregut

yolk sac

yolk sac

hindgut

ductus omphalo-entericus

szik-hólyag

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membrana cloacalis

cloaca

hindgut

allantois

body stalk

yolk sac

ductus omphalo-entericus

cardiogenic area

esophagus

stomach

pharyngeal gut

ductus thyreoglossus

membrana buccopharyngea

lung

midgut

foregut

flexura duodenojejunalis

flexura coli sinistra

cecum

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Liver development

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Figure 14-9 Development of the liver, gallbladder, pancreas, and their duct systems from endodermal diverticula of the duodenum. The liver bud sprouts during the 4th week and expands in the ventral (anterior) mesentery. The cystic diverticulum and ventral pancreatic bud also grow into the ventral mesentery, whereas the dorsal pancreatic bud grows into the dorsal mesentery. During the 5th week, the ventral pancreatic bud migrates around the posterior side (former right side) of the duodenum to fuse with the dorsal pancreatic bud. The main duct of the ventral bud ultimately becomes the major pancreatic duct, which drains the entire pancreas.

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Figure 14-14 Formation of the liver and associated membranes. As the liver bud grows into the ventral mesentery, its expanding crown makes direct contact with the developing diaphragm. The ventral mesentery that encloses the growing liver bud differentiates into the visceral peritoneum of the liver, which is reflected onto the diaphragm. This zone of reflection, which encircles the area where the liver directly contacts the diaphragm (the bare area), becomes the coronary ligament. The remnant of ventral mesentery connecting the liver with the anterior body wall becomes the falciform ligament, whereas the ventral mesentery between the liver and lesser curvature of the stomach forms the lesser omentum.

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Tissue-tissue interactions between the cardiogenic mesoderm and the endoderm, mediated by

Fgf

and

Bmp

signals, induce hepatocytic markers within the endoderm (e.g.,

Albumin

and

Alpha fetoprotein

) while suppressing pancreatic development by upregulating

Shh

expression.

induction (SHH, cardiogenic mesoderm):BMP (2, 4, 7), FGF

(1, 2, 8),

Wnt, GATA4, Hnf3, C/EBP

Hex (hematopoietically expressed homeobox) essential for the hepatocyte differentiation

cell differentiation, mesoderm, endothel migration:

Notched / Jagged1,(Alagille syndrome)

Vegf, BMP, FGF

adult liver functions (albumin, alfa fetoprotein synthesis):

Hnf (hepatic nuclear factor family)

C/EBP, Egf, Hgf, Tgf

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Sites of hematopoiesis in the human embryo. The

graph

highlights the relative importance of the various sites of hematopoiesis. AGM, aorta/genital ridge/mesonephros region. (Based on Carlson B:

Patten's foundations of embryology

, ed 6, New York, 1996, McGraw-Hill).

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regeneration capacity of the liver cells

Figure 18.29.

Kinetics of DNA synthesis in the four major cell types of the mammalian liver. It is possible that, since the hepatocytes respond fastest, they are secreting paracrine factors that induce DNA replication in the other cells.

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Pancreas development

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Figure 14-9 Development of the liver, gallbladder, pancreas, and their duct systems from endodermal diverticula of the duodenum. The liver bud sprouts during the 4th week and expands in the ventral (anterior) mesentery. The cystic diverticulum and ventral pancreatic bud also grow into the ventral mesentery, whereas the dorsal pancreatic bud grows into the dorsal mesentery. During the 5th week, the ventral pancreatic bud migrates around the posterior side (former right side) of the duodenum to fuse with the dorsal pancreatic bud. The main duct of the ventral bud ultimately becomes the major pancreatic duct, which drains the entire pancreas.

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dorsal pancreas bud (c

orpus és cauda pancreatis

)

duodenum

pancreas ventrale dexter (

: caput pancreatis és proc. uncinatus

)

pancreas ventrale sinister (

regrediated

)

liver bud

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Pancreas buds induction: aorta, Pdx1 homeobox genesPancreas / blood vessel

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Figure 14-10 Initiation of pancreatic development in a day 10 mouse embryo. Pancreatic development begins with the formation of endodermal buds projecting into the splanchnic mesoderm near the stomach-duodenal border.

Pdx1

is expressed (seen here by immunostaining in green) in both the dorsal and ventral pancreatic bud endoderm.

Glucagon

-positive cells are also detected at this early stage (cells in red) within the pancreatic endodermal buds.

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Tissue-tissue interactions between the cardiogenic mesoderm and the endoderm, mediated by

Fgf

and

Bmp

signals, induce hepatocytic markers within the endoderm (e.g.,

Albumin

and

Alpha fetoprotein

) while suppressing pancreatic development by upregulating

Shh

expression. The homeoprotein pancreatic/duodenal marker, Pdx1, promotes pancreatic development. However, in the presence of Shh, pancreatic development is repressed.

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Fig.8. Model of beta-cell development. In beta-cell precursors, Ngn3 induces the expression of Pax4; these cells also express Nkx2.2 and Nkx6.1, and shortly

thereafter, they express Islet1 and Pax6. The parallel activities of Pax4 and Nkx2.2 enable the program of

beta

-cell differentiation, and as a result, the level of

Pdx1 increases; the expression of HB9 is induced; and the synthesis of insulin ensues. In fully mature

beta

cells, the activity of Pax4 is no longer required.

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IrodalomScott F. Gilbert: Developmental Biology (7th edition, Sinauer Associates, 2003)Gary Schoenwolf: Larsen's: Human Embryology (4th edition, Elsevier, 2009)

Thomas W. Sadler: Langman's Medical Embryology (10th edition,

Lippincott Williams and Wilkins,

Philadelphia

,

2006)

Carlson BM. Human Embryology and Developmental Biology (Mosby, Philadelphia, 2004)