Download PG1007 Lectures 9 and 10 Development of The Digestive System

TR056/PG1007 Lecture 10 and 11 Development of The Diges@ve System-­‐1 Dr. Neil Docherty My Teaching Objec/ves To explain the broad relevance of the digestive tract to human
physiology
To illustrate how the growth and maturation of the digestive
tract depends on the development of an endodermal mould
generated by folding of the embryo
To outline the fundamental aspects of the temporal, spatial and
molecular control of foregut, midgut and hindgut development
Components of The Digestive System
Embryology describes the gut
in three regions;
-PHARYNGEAL GUT
Not covered here, development of pharynx
and related glands
FOREGUT
Oropharyngeal membrane to liver bud level
of duodenum (inc. liver and pancreas)
-MIDGUT
From liver bud as far as 2/3 of the length of
the colon
-HINDGUT
the last 1/3 of the colon to the cloacal membrane
Digestive System Functions
General Features of Digestive Tract Wall
EPITHELIUM
VASCULAR AND LYMPHATIC
ENDOTHELIUM
LYMPHOID TISSUES
LEUKOCYTES
CONNECTIVE TISSUE
NERVE PLEXES
SMOOTH MUSCLE
The cartoon illustrates the structure of
the distal part of the foregut, the duodenum
With a number of specialised features
However general wall structure has
Significant commonality from oesophagus
to rectum.
Origin of The Gut Tissues
WEEK 3
ECTODERM
MESODERM
ENDODERM
• Lining
• Muscle, vessels, immune component
connective tissue
• Enteric Nerves
Sagittal Midline Sections of Embryo
(Day 17-28)
17d
22d
28d
24d
Foregut
Hingut
Growth in the head and tail region leads to cephalocaudal folding
Lateral Folding and Body Wall Closure
Lateral folding of the embryo proceeds to body wall closure
by end of week 4
Suspension of Parts of The Gut Tube
From Dorsal Mesenteries Persists
Through Development
Enveloping of regions of the gut tube leads to their designation as
INTRAPERITONEAL
Traffic of vessels and nerves to and from the gut occurs via the mesenteries
Endodermal Lining of Digestive Track
(Week 4 and Week 5)
Primitive Mesenteries and Gut Vasculature
Both are derived from the visceral mesoderm
• Regional Mesenteries
• Regional Vascular Perfusion
-Input
-Drainage (veins/lymphatics)
• Autonomic Nerves
Neural Crest Cells (NCC) Give Rise to
Myenteric Nerve Plexuses
N.B. Interstitial cells of Cajal are also NCC derived
How Are Different Regions Specified?
Molecular Regulation
• Specification occurs during lateral body wall folding
• Defined by the activity of specific transcription factors
• Reciprocal inductive events occur between endoderm
and mesoderm (epithelial-mesenchymal)
e.g.
CSOX2- OESOPHAGUS, STOMACH
PDX1-PANCREAS DUODENUM
CDXC-JEJUNUM-ILEUM
CDXA-LARGE INTESTINE AND RECTUM
Sonic Hedgehog and HOX Gene Cascades
In Midgut and Hindgut Specification
Remember the colinearilty of
HOX gene expression and
Anterior-posterior patterning?
Reciprocal inductive phenomena
Foregut 1.
Oesophagus
LATERAL
VENTRAL
Diverticulum formation
Septum formation
Partitioning
Oesophageal lengthening
WEEK 4
WEEK 5
Foregut 2: The Stomach
Appears as a dilatation of the foregut
Position and size altered by growth and rotation
ANTERIOR
VIEW
TRANSVERSE
VIEW
FINAL AXIS IS
ABOVE LEFT
TO BELOW RIGHT
SAGITTAL VIEW
OF REGION
The Duodenum
• Caudal region of the foregut and the cephalic region of the midgut
• C-shaped loop secondary to stomach rotation
• Dorsal mesoduodenum presses on dorsal body wall and peritoneal
fusion occurs rendering the duodenum retroperitoneal in position
SAGITTAL
TRANSVERSE
The Liver and Gall Bladder
Arise from endodermal outgrowth of the distal foregut
LIVER DEVELOPMENT
1.  Hepatic diverticulum-some cells from outgrowth invade septum
transversum and form biliary tree
2.  These cells along with mesoderm derived cells complete the liver
structure
3. Remainder of cells from the diverticulum that do not invade septum
form;
•  bile duct
•  cystic duct
•  gallbladder
Week 3 to 4
The Pancreas
• Formed by 2 endodermal buds from duodenum (dorsal and ventral)
• SHH Signalling silenced by FGF
• Switch on PDX1 programme
• Stomach rotation, C-shaped alignment of duodenum and
posterior shifting of bile duct brings buds close together
Stomach rotation
Duodenal rotation
Posteriorisation
of bile duct and
ventral bud
Fuses with inferior
Surface of dorsal
pancreas
The Midgut
• Distal to the entrance of the bile duct into the duodenum
• Through the first 2/3 of the large intestine
• Begins as a loop the apex of which contacts the yolk sac
• Cephalic limb
• -distal duodenum
-jejunum
-proximal ileum
• Caudal Limb
-distal ileum
-cecum
-appendix
-ascending colon
-2/3 of transverse colon
Counterclockwise Rotation
LOOP DYNAMICS
-Rapid preferential growth of cephalic limb
Leads to;
-Rotation of cephalic limb below caudal limb
-physiological herniation (weeks 6 to 10)
270°
(when viewed from front looking down the
vitelline duct lumen)
Physiological Herniation
Final Positioning of Intestinal Loops
The Gut
Loops and Mesenteries
At some points the gut
Is intraperitoneal
-e.g. jejunal loops
At others points
it is retroperitoneal
-e.g. ascending colon
The Hindgut
• Distal 1/3 of transverse colon
• Sigmoid colon
• Rectum
• Upper part of anal canal
enters
Posterior region of the cloaca
Opening of Cephalic and Caudal Ends of Gut
Cephalic end
FOREGUT
Caudal end
HINDGUT
Ectodermal/endodermal membrane
OROPHARYNGEAL MEMBRANE
Rupture in week 4
Ectodermal/endodermal membrane
CLOACAL MEMBRANE
Rupture in week 7
Open cavity at cephalic end of primitive gut
-ORAL CAVITY-ECTODERM LINED
Open cavity at caudal end of primitive gut
-ANUS-ECTODERM LINED
Today’s Learning Objec/ves Your learning from lectures 9 and 10 should focus on
being able to;
1) Integrate the relevance of the digestive tract to human
physiology
2) Chart and describe how the growth and maturation of the
digestive tract depends on the development of an endodermal
mould generated by folding of the embryo
3) Describe and integrate the fundamental aspects of the
temporal, spatial and molecular control of foregut, midgut and
hindgut development