L4 - Endoderm derivatives: respiratory and digestive system

Question 1

origin of endoderm

Answer 1

primitive (hypoblast - blood supply) vs definitie endoderm

do not contribute to embryo proper

Question 2

derivatives of the endoderm

Answer 2

digestive system = esophagus stomach intestine

secretory cells
mucus - goblet cells in trachea
surfactant
hormones
pepsin - digestive molecules
major organs = liver pancreas

endocrine glands = thyroid thymus endocrine pancreas

respiratory system lungs trachea gills

absorptive cells
ciliated cells - mucus transport in trachea/bronchi

stem cells basal cells in trachea
embryonic structures = allantois, vitelline duct

Question 3

the folding of the embryo

Answer 3

2 axes of folding:

1. craniocaudal- head and tail curling inward
   = heart and septum transversum
2. lateral amnion and lateral part of embryo overgrow and fuse ventrally
   = gut tube, coelem and amniotic cavity

Question 4

folding of the gut

chicken mouse

Answer 4

early =
anterior intestinal portal moves posterior

later
gut folding starts posterior caudal intestinal portal

AIP and CIP meet at midgut
yolk stap = vitaline duct

yolk stalk formed from originally anterior ventral endoderm

dorsal and ventral endoderm are out of phase with respect to their original location

Question 5

extra embryonic membranes

Answer 5

yolk = oldest extraembryonic tissue

umbilical cord formed from
vitelline duct and yolk sac from the embryo
connecting stalk from the placenta
surrounded and brought together by. the amnion

Question 6

consequences of problems in folding

Answer 6

1. Omphalocoele
   incomplete seperation of midgut from yolk sac
   intestine protrudes into belly button
2. Gastroschisis
   incomplete fusion of body wall
   coelom is open
   intestine protrudes outside of body

Question 7

formation of the digestive tube

Answer 7

endoderm folds along midline - lateral folding = left n right side brought closer together

fusion of endoderm ventrally = tube

fusion of splanchnic mesoderm ventrally = separation of gut from yolk

Question 8

fusion of gut and heart

Answer 8

foregut + heart development are linked

failure of foregut fusion = cardia bifida = failure of heart tube to close prperly

Question 9

formation of mouth and anus

Answer 9

MOUTH = early

head region folds forwards

anterior ectoderm contacts endoderm = stomodeum

fusion of ectoderm and endoderm = mouth

ANUS = late

at posterior (@organiser/node) endoderm contacts ectoderm
fusion = anus

Question 10

foregut midgut hindgut

Answer 10

pharynx oesophagus stomach duodenum
small intestine
large intestine

Question 11

gut division based on arterial supply

Answer 11

foregut derivatives supplies coeliac artery

midgut derivatives supplied by superior mesenteric artery

hindgut derivatives supplied by interioi mesenteric artery

Question 12

AP patterning of the early gut tube

Answer 12

Ent antagonists = repress hindgut

Wnt, FGF BMP and RA
repress forgut maintain hingut
from posterior mesoderm = primative streak

repress foregut fate and promote hindgut fate

Question 13

mesoderm patterns in endoderm

POSTERIOR DOMINAnCE

Answer 13

posterior endoderm cannt be anteriorised by contact with anterior mesodem

but anterior endoderm CAN be POSERIORISEd to be forced o change to posterior by contact wih posterior mesoderm

grafted tissue

Question 14

histogenesis of the intestine

Answer 14

stratified one cell thick epithelium of intestine
pattern of villus and intervillus domains ue to folding

endodermis cells get associated with mesenchymal cells - remian associated with illus tip

crypt formed but intervillus

Question 15

genetic lineage tracing

Answer 15

label all cells we think are produced by stem cells in the gut

Cre recombinase modifies DNA

take the coding sequence of Cre
knock it into a gene that we know is expressed in the stem cells
i.e Lgr5
now Cre is expressed whenever Lgr5 is expressed

Reporter allows us to visualise this i.e. LacZ
is transcribed
trranslaion is blocked by stop codon
Cre removes stop codon

permanent lineage tracing
will carry on expressing the Reporter
turn blue in colour range

Crept stem cels and their derivatives can be traced wth the genetic marker Lgr5

Question 16

stem cells and differentiation ingut

Answer 16

regulated by Wnt BMP Ephrin

cell fate controlled by notch signalling
high = enterocyte lineage
low = paneth lineage goblet endocrine

Question 17

making a gut in a petri dish

Answer 17

induced puripotent stm ces can be differentiated into intestinal organoids

make the cells become definitive endoderm
confirmed with sox expression

regionalise the endoderm
posterior identity
expression of posterior marker CDX2

growth in 3d

= test system for drugs

regenerative medicine

Question 18

organs and glands bud off from digestive tube

Answer 18

thyroid,saliv gland parathyr + thymus - pharynx

esophagus - trachea/lungs

duoderm - liver pancreas

large intestines - allantois

Question 19

lung liver and ventral pancreas are induced by signals from mesoderm

Answer 19

wnt signalling for induction of the lung

fgf from heart + bmp from septum = liver

absence of signals = central pancreas formation

Question 20

lung development

Answer 20

trachea and lungs from ventral foregut:

bud from endoderm
Wnt2 singalling
branching 
proximal airways
distal alveoli
embryonic phase

separation from gut tube
control of branching riven by fgf dignalling from lung mesenchyme

fgf induces endoderm outgrowth = induces expression of fgf antagonists and Shh in the endoderm = inhibits Fgf10 expression

airways and alvoli generation

airways first them alveoli
differentiates cells emerge

Question 21

cell types and lineage in the lung

Answer 21

proximalairways 
neuroendocrine cells
goblet cells
secretory claracells
ciliates cells

distal
alveoli
type 1 and 2 alveloar epithelial cells

Question 22

budding of the liver

Answer 22

hepatoblast lined liver bud

delamination an migration of heptoblasts into septum transversum
controlled by Prox1 transcripion factors

mesenchymal signals = HGF heptocte growth factor

bile duts formed from heptoblasts in close contact w portal mesnchyme colse to portal vein

Question 23

the pancreas

Answer 23

dual developemtal origin
dorsal and ventral pancreatic bud

2 functions
exocrine - digestive enzymes
endocrine - hormones controlling metabolism

cell types:
duct cells - exocrine form ducts
acinar cells - exocrine secrete igestive enzymes
islets - endocrine secrete hormones
mesoderm derives pancreatic mesenchyme

Question 24

pancreas development

Answer 24

From the posterior foregut endoderm near liver

2 buds initially:
ventral and dorsal bud

• pancreatic transcription factors Pdx1 + Ptf1a
• dorsal: interaction with notochord required for bud formation
  Activin +fgf - suppression of Shh exp in pre pancreatic endodeem

fusion of dorsal aorta separates notochord and foregut endoderm
mwsoderm derived retinoic acid required
ventral bud translocates to dorsal side - fused pancreas

pancreas has exocrine and endocrine fucntion
transcription factors determine cell fate
Nkx6 and Pax4 jointly specify insulin producing cells

= pancreatic progenitor cells

Question 25

cure for type 1 diabetes

Answer 25

lack of islet cells
controlled differentiation of ES or iPS cells into B cells
utilisees the signals and transcription factors that control normal cell lineage

invitro differntited b cells reduce hyperglycaemia in mouse models

Question 26

summary

Answer 26

AP patterning by posteriorising signal from the mesoderm
subdivision in foregut midgut and hindgut

signalling from the anterior mesenchyme Wnt heart Fgt and septum transversum BMP induces lungs liver an pancreas

local signalling and transcriptional control determine further cell fate within each oran