Lecture 8: The Pharyngeal arches

Question 1

neural induction

Answer 1

neural and surface ectoderm become different

Question 2

neurulation

Answer 2

process that delivers the neural tube when neural plat rolls up into a neural groove then dorsal lateral hinge points appear and at junction to the surface ectoderm you have the neural folds = neural tube

Question 3

neural crest cell emigration

Answer 3

msynchymal cells under surface ectoderm - crawl over neural tube then move away from it
= neural crest cells
come from crest of the fold at the border between the surface ectoderm and neural tube

Question 4

placodes

Answer 4

ectodermal thickenings that give rise to sense organs and nerves belonging to the PNS

otocyst - cup - pit - ectodermal placode

Question 5

pharyngeal branchial gill arches

Answer 5

ventral side of embryo
confined to head
segmented
5-6 weeks human embryos
caudal to the mouth
jawwed= 7
jawless - 9 
hagfish - 15

swellings around lateral and ventral side of pharynx

first arch - maxillary
second - mandibular
structure
endoderm - pouch
endoderm - cleft/groove invagulates and meets endoderm
aortic arch endothellum and mesynchyme filling space between those tissues

Question 6

parts of pharyngeal arches

Answer 6

ECTODERM
inner ear vesicle lines up with second pharyngeal arch

distinct thickenings in ectoderm = epibranchial placodes = deliver sensory of facial 7 glossopharyngeal 8 and vagal nerves 9

ENDODERM

arch mesenchyme surrounds blood vessel fills space between endoderm and ectoderm is not homogenous

MyoD expressed in the core of pharyngeal arches and close to the aortic arch blood vessel

Question 7

which cells contribute to the arch mesenchyme and what do the cells give rise to

Answer 7

do fate mapping experiments

see what the neural crest cells do= deliver pigments cells to skin nodes of entry in the sympathetic and parasympathetic
neural crest cells deliver the arches connective tissue and the skeleton inc. the jaws

Question 8

head mesoderm

Answer 8

makes head skeletal muscle

neural crest cells deliver connective tissue n tendons for the muscle and pharyngeal arch cartilage and bone

Question 9

what are the cones the arch neural crest give rise to

Answer 9

midbrain + forebrain neural crest migrate rostrally = frontal nasal facial bones

caudal midbrain to caudal rhombomeres of hindbrain there are streams of neural crest cells that migrate laterally into the pharyngeal arches
1st archL macels cartilage - mandible. malleus

2ndstapes, hyoid
3rd

Question 10

layout

Answer 10

surface ectoderm - delivers placodes - sensory nerves

pharygneal endoderm- pharyngeal glands

neural crest cells = skeleton cartilage

mesoderm delivers blood vessels and craniofacial skeletal muscle
aortic arch

Question 11

stage vertebrates look most similar

Answer 11

= phylotypic stage

are they homologous
develop in same way
give rise to same structures
only in vertebrates

Question 12

how far down the chorsate tree can we go and find pharyngeal arches with a neural crest derived skeleton

Answer 12

neural crest cells were there to give pigment to the skin only in vertebrates do they build skeleton
not present in non vertebrates

ecto-mesenchymal crest = derivatives on neural crest cells:
gilia cells
pigments cells
connective tissue fibroblasts
cartilage
ost - bones
odontoblasts - make dentine of our teeth

Question 13

jawed vertebrates

Answer 13

skeletal elements in the arches are specialised
1st arch elements form the jaws

sensorimotor nerves
epibranchial ganglia
skeletal muscle
skeletal elements
gill slits

the jaw is mobailsed by head mesoderm skeletal muscle

each arch has its placodes

sensor neurons stimuate muscle contraction

Question 14

how is the visceral skeleton pharyngeal arch skeleton made from ecto-mesechymal neural crest cells

how do cells know they should be skeletogenic neural crest cells

Answer 14

AP2 alpha neural crest marker markers cells as they emigrate

Sox10 marks newly formed

Foxd3 = marks neurogenic neural crest cells

Sox10 and Foxd3 marks are turned off when the cells enter the pharyngeal archs

therefore migrating neural crest cells express AP2 alpha all the time
immature express sox
neurogenic express dlx2

as neural crest cells enter the pharyngeal arch
fgf8 expressed in the pouches trigger ectomesynchymal fate and should start to express dlx2

when neural crest cells are made insenstive to energy they are harbouring the dominant negative
they migratepst the fgf pouches wihtout giving up their neurogenic program they do no become ecto mesynchymal but they keep on being naive bias towards being neurogenic
the normal wild type cells are able to active fgf cascade when passing fgf pouches they become specified

Question 15

what tells cells how far dorsal or ventral they are to make articulated bony elements reaching round the pharynx

Answer 15

dorsal cells will only have expression dlx 1 and 2

cv
entrals will also have dlx 5 and 6

overlapping expression of dlx 1 and 2 is nnecessaryfor the sspecificationof the lateral

Question 16

tells 1st arch from the other archs to make jaws - rostrocaudal positional info

Answer 16

Hoxa2 genes
the further away from the 3 prime end the 7th pharygeal arch
the later the more caudal expression of the gene

the first arch doesnt express the hox gene

the rostral region of the brain and first arch express the transcription factor Dlx2

hypothesis :
overlapping hox gene expression specifies the caudal an posterior arches and absense of hox genes specifies the first arch
hox genes specify the posterior arches
absence of hox gene expression specifies the first arch

test: knock out hox genes, expect anterior transformation misexpress Hox, expect posterior transformation

in mice

hox genes as hox a2 are not expressed in the first arch = mandibular arch

loss of hoxa2 leads to
1. duplication of first arch structres
partial loss of 2nd arch sturctures

conc hox proteins make the posterior arches different from the first

overlapping hox gene expression specifies he second and the more posterior

Otx2 transcription factor gives rise to the maxillary and mandiular

Question 17

neurocranium the brain case

crown grathosome

Answer 17

compound structure
made up of:
1. from ecto- mesynchymal cells = fronto-nasal neural crest cells - facial bones

2. head mesoderm
3. occupital somites / modified vertebrae

Question 18

skull development

Answer 18

primary palate
maxillary competent of first pharyngeal arch and the frontal nasal
maxillary fuses w frontonasal elements of neurocranium to form upper part of face

failure of fusion between maxillary and medial nasal swelling lateral + medial nasal swelling = cleft lip

Question 19

only in mammals a secondary palate will form

Answer 19

secondary palate = part of skull vault that separates the oral and nasal cavity

swelling on either size of the maxillary - grow out n fuse = palatal shelves
failure of the fusion of the shelves = cleft palate

Question 20

fusion of skull plates

Answer 20

areas between bony plates

fgf signalling promote osteogenic differentiation
immature ostoblaston the outer edge of the mineralised osteoid express fgf1

bone maturation
proliferation
recruitment
diferentiation 
apoptosis

signalling through receptor 2 and 3 keeps cells mitotically active and undifferentiated keeping suture open
eventually fgf levels rise above a threshold = all the cells complete differentiation = sutures fuse = skull bone differentiation

mesoderm an neural crest cells derived portions of the skull vault do not fuse for a prolonged period of time to accomodate for brain growth

Question 21

gain of function mutation

fgf related craniosynostosis

Answer 21

premature fusion of sutures = skull defects craniosynostosis
mutations cause fgfr recptior to initiate the signalling system without fgf ligand being present or overactivate the fgf pathway = more than normal fgf signalling

Question 22

how does notch delta signalling create a negative feedback loop

Answer 22

what molecular oscillations creates the on off state of notch delta signalling

Question 23

what in the segmentation of the paraxial mesoderm in the trunk creates the molecular clock

Answer 23

how do you create this on off state of notch delta signalling

when lunatic fringe is high it suppresses notch because it inactivates notch on the cell membrane and even if not were to interact with delta
notch will not be in the position to become processed and enter the nucleus there is nothing to activate lunatic levels goes down
as lunatic levels goes down the suppression of notch is relieved - notch when it touched delta it can engage in this cascade where it will activate lunatic and bring about repression again