Download Gut Development

The Evolution and
Development of the
Gut
Dr Mike Wride
School of Natural Sciences
Zoology Department
email: [email protected]
The gut?
• Gut Function and Regulation (Dr. Alan Tuffery)
• Absorption of nutrients (the digestive system)
• Structure of the gut:
• Anatomy
• Embryological Origin
• Development
• Comparative anatomy/development
Topics to be covered in
today’s lecture
• Early Development - gastrulation (a reminder)
• Endoderm
• Gut development and genetics
• Gut nervous innervation: Hirschsprung’s disease
• Gut evolution
Gut anatomy
Wikipedia: http://en.wikibooks.org/wiki/
Anatomy_and_Physiology_of_Animals/The_Gut_and_Digestion
Gut ultrastructure:
Small intestine Villi
Useful texts for gut
structure, physiology
and development
•
Developmental Biology 8th Ed. Scott S Gilbert.
Sinauer. Chapter 15 pages 493-499.
•
Vertebrates, Comparative Anatomy, Function and
Evolution. Kenneth V. Kardong. McGraw Hill 4th
International Ed. Chapter 13, pages 496-535
•
Animal Physiology. Hill, Wyse, Anderson. 2nd Ed.
Chapter 5, pages 111-142
Gastrulation: a reminder
• Gastrulation begins between days 14 and
16 of human development and at about
E6.5 in the mouse
• Gastrulation results in formation of the 3
germ layers: mesoderm (e.g. muscle, bone,
kidneys), endoderm (e.g. gut) and ectoderm
(e.g. nervous system/epidermis)
Gastrulation cont...
Figure 11.34. Gilbert Chapter 11, page 354
•
•
Endoderm forms
gut is derived from endoderm
Endoderm
• 1: Induces several mesodermal tissues
(notochord, heart, blood vessels, germ layer)
• II: Constructs linings of 2 tubes of vertebrate
body plan: Digestive tube and respiratory tube
i.e. both derived from primitive gut
• Buds from digestive tube form: liver,
gallbladder, pancreas
• Region of digestive tube anterior to
respiratory tube: called the pharynx
Formation of the
Human Digestive
System at (A) 16
days (B) 18 days
Formation of the Human Digestive
System at (C) 22 days (D) 28 days
Development of the
Pharynx
The digestive tube and
its derivatives
• Regional specification of the gut endoderm
and its derivatives
• Involves reciprocal interactions between
endoderm and mesoderm
does this ring a bell?
Regional specification
of gut
• Digestive tube meets different kinds of
mesenchyme (splanchnic lateral plate
mesoderm) at different levels (rostral-caudal;
head-tail)
• Digestive tube differentiates into different
kinds of structures: oesophagus, stomach,
small intestine, large intestine and colon
• There is an emerging consensus on the steps
leading to regional specification of gut tube
The role of Barx1 in
gut development
Kim BM, Buchner G, Miletich I, Sharpe PT, Shivdasani RA. The stomach
mesenchymal transcription factor Barx1 specifies gastric epithelial identity
through inhibition of transient Wnt signaling. Dev Cell. 2005 Apr;8(4):611-22.
-/- Barx1 knockout mouse
BMP signaling influences
development of muscle types
Theodosiou NA, Tabin CJ. Sox9 and Nkx2.5 determine the pyloric sphincter epithelium under the
control of BMP signaling. Dev Biol. 2005 Mar 15;279(2):481-90.
Liver pancreas and gall
bladder
Nervous innervation of the
gut - Hirschsprung’s disease
•
Enteric nervous system (ENS): provides intrinsic innervation
of the gastrointestinal tract
•
Controls essential functions such as motility, secretion and
blood flow
•
Comprises a vast number of neurons and glial cells organized
into complex networks of interconnected ganglia distributed
throughout the entire length of the gut wall
•
Hirschsprung’s disease (congenital aganglionic megacolon): 1in
5000 babies - enlargement of colon caused by bowel
obstruction resulting from an aganglionic section of bowel
(the normal enteric nerves are absent)
Arrangement of the ENS
Farlie et al Birth Defects Research (Part C) 72:173–189 (2004)
The Neural Crest
Enteric neurons and
glia - derived from
neural crest cells
(undergo extensive
migration,
proliferation,
differentiation and
survival to form a
functional ENS).
Migration paths of neural
crest cells to colonize the gut
Farlie et al (2004)
Farlie et al (2004)
Holschneider and Puri (2008)
Comparative Gut
Anatomy/Evolution
• Symbiosis with heterotrophic microbes provide metabolic capabilities that the
animal lacks
• Include anaerobic bacteria, protists, yeasts,
fungi carrying out fermentation
• Development of specialised enlarged/
dilated gut chambers during evolution
Foregut fermenters:
ruminant mammals
1. fermentation - of non digestible compounds
2. Synthesis of B vitamins and essential amino acids
3. Recycling of waste nitrogen (urea) to make
proteins
Hindgut fermenters
Similar to foregut fermenters in terms of fermentation but vitamin synthesis and nitrogen
recycling do not occur to the same extent
Variations in the stomach and
intestines of lower vertebrates
and birds
Variations in the stomach and
intestines of mammals
Stomachs of Various Vertebrates
Summary of Today’s
Lecture
• Early Development - gastrulation (a reminder)
• Endoderm
• Gut development and genetics
• gut nervous innervation: Hirschsprung’s disease
• Gut evolution