Molecular Embryology and Trunk Development - Reverse Flashcards
High BMP4 and low Shh
surface ectoderm induced by
Intermediate BMP4 and Shh
neural crest induced by
low BMP4 and high Shh
neural tube induced by
specifies neural crest cell fate/promotes cells migration
SNAIL/SLUG
BMP4 concentration gradient
specification of the mesoderm
high BMP4
lateral plate mesoderm (lpm) IB
intermediate BMP4
intermediate mesoderm(im) IB
low BMP4, differentiates into somites
paraxial mesoderm (pm) IB
transcription factors responsible for craniocaudal body segmentation, e.g. Hoxa1, Hoxd13
Hox proteins
4 chromosomes, 13 gene clusters that code for Hox proteins. Provide spatial/temporal colinearity of gene expression & development
homeobox genes
Cranial to caudal. RA (cranial) promotes Hox gene expression. FGF8 (caudal) inhibits Hox.
Somite development order
located where RA signal overpowers FGF8 signal
someite differentiation front
induces paraxial mesoderm to form somites via Hox. intercellular signaling molecule that guides development of the posterior portion of the embryo.
RA
from notocord induces sclerotome
Shh (effect on mesoderm)
from neural tube/surface ectoderm induces myotome
Wnt (effect on mesoderm)
from neural tube induces dermatome
NT-3 (effect on mesoderm)
part of a somite that forms the muscles of the animal. cells express MyoD or Myf5.
myotome
differentiate into dermis. the dorsal portion of the paraxial mesoderm somite which gives rise to dermis.
dermatome
SHH -> Pax1
scleratome (signal + TF)
WNT -> MRF (Myf5 + MoyD)
myotome (signal + TF)
NT-3 -> Pax3
dermatome (signal + TF)
a secretory protein that induces lateral plate mesoderm to form left-side structures by promoting expression of Pitx2.
NODAL
responsible for the establishment of the left-right axis, the asymmetrical development of the heart, lungs, and spleen, twisting of the gut and stomach, as well as the development of the eyes. locally expressed in the left lateral mesoderm, tubular heart, and early gut which leads to the asymmetrical development of organs and looping of the gut.
Pitx2
BMP4 from ectoderm promoting expression of Pax 3 & Pax 7
dorsalization
Shh from the notocord antagonizes BMP4 (represses Pax 3 & Pax 7)
ventralization
promotes migration of neural crest cells
SLUG
signaling molecule secreted by the lateral plate mesoderm required for the early differentiation of the embryo and establishing of a dorsal-ventral axis. It is secreted from the dorsal portion of the notochord, and acts in concert with sonic hedgehog (released from the ventral portion of the notochord) to establish a dorsal-ventral axis for the differentiation of later structures as well as inducing posterior neural tube (sensory)
BMP4
FGF8 cause cilia that preferentially sweep toward the left sidethat activates NODAL which induces LPM to promote Pitx2 induced left side development.
left-right asymettry
releases NODAL. Where invagination occurs.
primitive node
expression at primitive streak controls cell migration
FGF8
form skeletal muscle in head, don’t dorm bony structures that come from somites. form on sides of cranial neural tube. do not segregate into sclerotome, dermatome, and myotome.
somitomeres
differentiate into axial skeleton. cells express PAX1.
sclerotome
induces sclerotome development
SHH and Noggin expression
myotome posterolateral origin. MyoD expression. body wall and limb muscles. anterior primary rami.
hypaxial division
myotome posteromedial origin. Myf5 expression. intrinsic back muscles. posterior primary rami
epaxial division
begins in utero by 7 weeks. primary centers form by 7 weeks and are active until age 6. secondary ossification is complete around 25 years of age. at birth vertebrae consist of three bony parts united by cartilage.
ossification
form from notochord and mesenchyme of somites. notochord forms nucleus pulposus. mesenchyme forms anulus fibrosus
intervertebral discs
occurs as each vertebra forms from the fusion of the caudal half of the sclerotome of one somite and the cranial half of the sclerotome of the subjacent somite. somites surround neural tube and notochord.
resegmentation
visceral mesoderm, initally between somites and finish at mid-vertebrae.
intersegmental arteries
outgrowth of neural tube, initially at mid-somite, finish between vertebrae.
spinal nerves
come from paraxial mesoderm, initially within somite and finish to span vertebrae, allowing for movement of the vertebral column)
myotomes
bony part derived from sclerotome portion of paraxial mesoderm. cartilaginous part derived from sclerotome cells that migrated.
ribs
derived from parietal layer of lateral plate mesoderm.
sternum
right and left halves do not fuse appropriately.
cleft sternum
loss of function mutation of various Hox genes, can lead to accessory cervical or lumbar ribs.
accessory, forked, or fused ribs
malformations of the spine resulting in wedge-shaped vertebrae that can cause an angle in the spine (such as kyphosis, scoliosis, and lordosis).
hemivertebra
fracture of pars interarticularis due to congenital developmental defects or trauma
spondylolysis
dislocation between adjacent vertebrae subsequent to spondylolysis.
spondylolisthesis
ancephaly, spina bifida, rachischisis. Can be indicated pre-birth with a-feroprotin increase inmaternal serum tests.
failure of neuropores to close results in:
severe caudal failure, in which neural tissue is exposed and often becomes necrotic)
rachischisis
intake prior to and during pregnancy can decrease incidence of neural tube defects by as much as 70%
folic acid supplement reason
lateral plate, intermediate, paraxial. Driven by BMP4 concentration gradient.
mesoderm differentiation
induces ectoderm to form neuroectoderm which undergoes neurulation to form neural tube and neural crest, then induces anterior neural tube (motor).
SHH
non-migratory myoblasts, i.e. back muscles.
epaxial derivatives
Spermreach oocyte, pass through CR. Acrosome reaction (male), Zona reaction (female). Sperm fuses with ocyte membrane, oocyte completes M2. Pronuclei fuse to from single diploid nucleus.
Day 1
Cleavage, compaction (day 4), cavitation, hatching, implantation (day 6)
Week 1
uteroplacental circulation, trophoblast differentiation (cytotrophoblast and syncytiotrophoblast.), bilaminar disc formation, chorionic cavity formation, hcG detectable day 8.
Week 2
ectopic pregnancy, placenta previa, molar pregnancy, choriocarcinoma.
Week 2 complications
Gastrulation, neurulation, NODAL expression, FGF8 expression, hypoblast displaced, body axes established, lateral body folding.
Weeks 3-4
forms urogenital system
Intermediate mesoderm
forms connective tissue of body wall and limbs
parietal layer of lateral plate mesoderm
GI/respiratory organs exxcept epithelial lining
visceral layer of lateral plate mesoderm
somites differentiate (wk 4), myotome differentiation (wk 5), resegmentation (wk 5), organogenesis
Weeks 4-8
chondrification centers for vertebral column develop
week 6
primary ossification centers for vertebral column develop
week 7
ribs form (sclerotome), tail regresses, limbs rotate/enlongate, digits and face develop,
week 8
produces floating ribs
hox9
prevents rib formation
hox 10
from parietal layer of lateral plate mesoderm
sternum formation
sacralization of vertebrae
Hox11
rostral neuropore doesn’t close
Anencephaly
causal neuropore doesn’t close
spina bifida
malformed pelvis, underdeveloped lower limbs, 250X more in pregestational diabetics
Caudal dysgenesis
form of CD, mermaid syndrome
Sirenomelia
Loss of function: ribcages with all ribs attacted to sternum
Mutation of Hox9
Loss of function: lumbar and sacral vertebrae with ribs. Gain of function: Thoracic vertebrae without ribs
Mutation of Hox10
LoF: Sacral vertevrae that donot fuse. GoF: vertebrae at various levels fusing
Mutation of Hox 11
fracture of pars interarticularis
Spondylolysis
Hox11 gain of function mutation at L5
Sacralization of L5 vertebra
bone ossification centers (wk 12), ext genetalia visible (wk 12), swallowing and urine formation (wk 10), respiratory movements (wk 15)
Weeks 9+ (fetal period)
weeks 24 - 28
Sound and light recognition