L4 - Endoderm derivatives: respiratory and digestive system Flashcards
origin of endoderm
primitive (hypoblast - blood supply) vs definitie endoderm
do not contribute to embryo proper
derivatives of the endoderm
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
the folding of the embryo
2 axes of folding:
- craniocaudal- head and tail curling inward
= heart and septum transversum - lateral amnion and lateral part of embryo overgrow and fuse ventrally
= gut tube, coelem and amniotic cavity
folding of the gut
chicken mouse
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
extra embryonic membranes
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
consequences of problems in folding
- Omphalocoele
incomplete seperation of midgut from yolk sac
intestine protrudes into belly button - Gastroschisis
incomplete fusion of body wall
coelom is open
intestine protrudes outside of body
formation of the digestive tube
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
fusion of gut and heart
foregut + heart development are linked
failure of foregut fusion = cardia bifida = failure of heart tube to close prperly
formation of mouth and anus
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
foregut midgut hindgut
pharynx oesophagus stomach duodenum
small intestine
large intestine
gut division based on arterial supply
foregut derivatives supplies coeliac artery
midgut derivatives supplied by superior mesenteric artery
hindgut derivatives supplied by interioi mesenteric artery
AP patterning of the early gut tube
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
mesoderm patterns in endoderm
POSTERIOR DOMINAnCE
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
histogenesis of the intestine
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
genetic lineage tracing
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
stem cells and differentiation ingut
regulated by Wnt BMP Ephrin
cell fate controlled by notch signalling
high = enterocyte lineage
low = paneth lineage goblet endocrine
making a gut in a petri dish
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
organs and glands bud off from digestive tube
thyroid,saliv gland parathyr + thymus - pharynx
esophagus - trachea/lungs
duoderm - liver pancreas
large intestines - allantois
lung liver and ventral pancreas are induced by signals from mesoderm
wnt signalling for induction of the lung
fgf from heart + bmp from septum = liver
absence of signals = central pancreas formation
lung development
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
cell types and lineage in the lung
proximalairways neuroendocrine cells goblet cells secretory claracells ciliates cells
distal
alveoli
type 1 and 2 alveloar epithelial cells
budding of the liver
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
the pancreas
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
pancreas development
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
cure for type 1 diabetes
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
summary
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
