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Medsci 312 > Lecture 10; Organogenesis 2 > Flashcards

Lecture 10; Organogenesis 2 Flashcards

1
Q

What are the endoderm derived organs?

A

Forgut

Midgut

Hindgut

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2
Q

What specifically does the endoderm form?

A
  • Lining of digestive and respiratory tract
  • Lining of accessory organs of the digestive
    tract: liver, gall bladder and pancreas
  • Thyroid
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3
Q

What is formed by the endoderm in the forgut;

A

Oesophagus, stomach, upper duodenum, liver, gallbladder, pancreas

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4
Q

What is formed by the endoderm in the midgut;

A

lower duodenum, jejunum, ileum, cecum, appendix, ascending colon, and first two-third of transverse colon

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5
Q

What is formed by the endoderm in the hindgut;

A

last third of the transverse colon, descending colon, rectum, anus

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6
Q

What is the function of the digestive system;

A

Digestion

Absorption

Excretion

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7
Q

What specifically happens in digestion?

A

Digestion

  • Mechanical – breakdown of food into small pieces (mouth, stomach)
  • Chemical – enzymatic digestion of food pieces into molecules (mouth, stomach, small intestine)
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8
Q

What specifically happens in absorption?

A

Absorption

Water and digested food pass into the bloodstream (small intestine – nutrients; large intestine – water, salt)

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9
Q

what specifically happens in excretion?

A

Excretion

Expulsion of undigested food (anus)

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10
Q

How do the germ layers contribute to the formation of the colon?

A

• Endoderm: Inner epithelial lining (mucosa)
• Mesoderm: Muscle, blood and lymph
vessels, connective tissue
• Ectodermal: Nerves

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11
Q

What are the features of the epithelium?

A
  • Polarity: apical, basal and lateral surfaces
  • Not vascularized → Nutrition via the basement membrane
  • Important for secretion, absorption, protection, sensing
  • Enlarged surface → microvilli (brushborder)
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12
Q

What are the types of epithelium?

A 
Simple Squamous (blood vessels and alveoli)
Simple Cuboidal (Kidney tubules)
Simple Columnar (digestive cells)
Stratified Squamous (skin, vagina)
Stratified Cuboidal (Ducts of seat glands)
Stratified Columnar (mammary glands)
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13
Q

Where does epithelium typically form;

A
  • Lines body surface, cavities, tubes and ducts
  • High turnover of cells, highly regenerative
  • Cells are tightly packed
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14
Q

What seals the epithelium?

A
  • Cells are tightly bound together via the junctional complex
  • Tight junctions: integral proteins of adjacent cells fuse together = impermeable

i.e cadherins, adherins, gap junctions

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15
Q

What is an impermeable barrier necessary?

A

Disruption of Barrier
• Bacterial or viral infection
• Exposure to toxins or physical insult
• Systemic diseases (e.g. IBD, leaky gut)

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16
Q

Describe the development of intestinal epithelium?

A

• Multipotent intestinal progenitor cells in the crypt give rise to all epithelial cell types.
• Zone of rapid proliferation
• Differentiation as the cells migrate up. Turnover: 3-4
days. Paneth cells migrate down, much slower turnover.

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17
Q

What are the cells of the intestinal epithelium?

A

Absorptive cells (enterocytes)
Goblet cells
Enteroendocrine cells
Paneth Cells

Formed from intestinal stem cells (proliferation in the crypts)

Differentiated cells form the villus

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18
Q

What is the function of enterocytes?

A

Enterocytes
Nutrient absorption, incl. sugar, amino- and fatty acids, ions, vitamins, water, via specific receptors and transporters located in the apical domain

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19
Q

What is the function of goblet cells?

A

Goblet cells

Mucus production Protection from HCl Lubrication

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20
Q

What is the function of endocrine cells?

A

Endocrine cells

Sensing and hormone secretion

21
Q

What is the function of paneth cells?

A

Paneth cells

Immune defence, Secretion of anti- microbial peptides

22
Q

How many types of endocrine cells are scattered through the intestinal tract?

A

15+ subtypes

23
Q

What exactly do these endocrine cells do in in the digestive tract and sense)?

A
  • Sensors for composition of luminal content and regulate the secretion of hormones accordingly
  • Receptors on the apical side, respond to fatty acids, amino acids, sugars, bile, calcium
24
Q

What do endocrine cells of the digestive tract release?

A

• Upon stimulation, hormones are secreted from the basal membrane

  • Systematic distribution via bloodstream - Direct activation of nerves
  • Paracrine signalling
25
Q

Whats an example of an digestive tract hormone?

A

Cholecystokinin (CCK)

26
Q

Where is Cholecystokinin (CCK) released from?

A

Stomach

27
Q

What causes the production of Cholecystokinin (CCK) and whats its function?

A
  • Produced in response to fat and protein
  • Inhibits the stomach from emptying
  • Stimulates secretion of bile and pancreatic
    enzymes to facilitate fat and protein digestion

→ modulates appetite

28
Q

What does exogenous CCK do?

A

Exogenous administration of CCK decreases meal size. But: effect is short-lived, as CCK degrades rapidly.

29
Q

What mediates patterning in embryonic development?

A

• Mediated by morphogens = secreted growth factors or chemicals that diffuse from a source and form a gradient

30
Q

What does the gradient of morphogens do?

A 
- Gradients of morphogens
induce
-  Cascades of transcription factors
regulate
-  Positional patterning of organs
31
Q

What is regionalisation;

A

Crosstalk between endo- and mesoderm
Mesoderm secretes morphogens, incl. FGF, BMP, Wnt
A-P patterning of the primitive gut tube, into broad domains

(foregut,midgut,hindgut)

32
Q

How are patterns translated into organs?

A

Transcription factors are induced along morphogen gradients

→ Broad domains are progressively refined into smaller domains where organs will form

33
Q

What are some examples of growth factors?

A

FGF2

RA

Wnt, FGF4, BMP

34
Q

Describe FGF2 expression;

A

FGF2

  • High: lung and thyroid
  • Low: liver, pancreas and small intestine
35
Q

Describe RA expression

A 
Retinoic acid (RA)
- High: lung, stomach, pancreas, liver - Defines midgut – hindgut boundary - Low: small and large intestine
36
Q

Describe Wnt, FGF4, BMP signalling

A

Wnt, FGF4, BMP

- Induce mid- and hindgut-derived organs

37
Q

What is a good animal model for embryonic development?

A

Zebrafish

38
Q

How related is the zebrafish to humans?

A
  • 70% of protein-coding human genes are related to genes found in zebrafish
  • 84% of genes known to be associated with human disease have a zebrafish counterpart
39
Q

What happens when zebra fish embryos were soaked in RA inhibitor?

A

Lower concentration of RA has shifted the small intestine segment further anterior

40
Q

Describe the formation of the intestinal epithelium;

A

• Antagonizing Wnt (proliferative compartment) and BMP (differentiated compartment) gradients establish the crypt – villus axis

  • Cell migration through zone of proliferation into differentiation
  • Crypts become the niche for stem cell maintenance

Wnt = development
BMP=maintainence

41
Q

Describe the differentiation of stem cells into enterendocrine cells;

A

Intestinal stem cell (multilineage potential)

MATH 1 (Secretory progenitor) (tri-lineage potential)

Ngn3 (early endocrine progenitor) (unilineage potential)

NeuroD (committed endocrine precursor)

Enteroendocrine cells

42
Q

What other cells can be formed instead in the endocrine fate lineage?

A

Notch signalling (acts between two fates) can cause these stem cells to form Enterocytes instead

Also MATH1 can form paneth / goblet cells instead of Ngn3

43
Q

Describe the signals that play a role in the stepwise endocrine fate of intestinal stem cells;

A

→ Transcription factors act sequentially to specify fates

→ Notch acts as a switch between two fates

44
Q

Describe the signals that play a role in the stepwise endocrine fate of intestinal stem cells;

A

→ Transcription factors act sequentially to specify fates

→ Notch acts as a switch between two fates

(fate restriction is that action of signals and transcription events reducing the potential of cells)

45
Q

How is the homeostasis of epithelium maintained?

A
  • Maintenance of a tissue during adult life
  • Epithelia – high turnover and regeneration → proliferation needs tight control

=signals!

46
Q

What are some examples of signals that maintain epithelium homeostasis?

A

Wnt: key factor for maintenance of the crypt / stem cells

Loss of Wnt → no crypts, small villi, all enterocytes
Gain of Wnt → ???

47
Q

What does hyperactive wnt sinalling lead to?

A

Mutation of APC gene, leads to over activation of Wnt→ uncontrolled proliferation at the expense of differentiation

48
Q

What is the most frequent cause of colorectal carcinoma?

A

Loss of APC

Medsci 312 (28 decks)

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