Embryo Limb Development Flashcards
where do the muscles of the limbs arise from?
Paraxial mesoderm
where do the limbs arise from?
somatic mesoderm
what weeks do the limbs form in
weeks 4-8
when are the basic structures of limbs (bones and muscle groups) established
between weeks 4-8
when do the fingers separate and ossification begins?
day 56
what germ layer does the limb bud come from
ectoderm and lateral plate (somatic) mesoderm
what germ layer do the bones, tendons, and vasculature come from
lateral plate (somatic) mesoderm
what germ layer do the muscles come from
paraxial mesoderm
when does the upper limb bud form
day 24
when does the lower limb bud form
day 28
what are the 3 axes of limb bud formation
proximal-distal
cranial-caudal
dorsal-ventral
what is proximal-distal growth controlled by
Apical ectodermal ridge (AER)
what is the AER necessary for
limb outgrowth
what is the AER sufficient for
Limb outgrowth
what is significant about removal of the AER at later stages
loss in more distal elements, less severe
what is significant about removal of the AER at earlier stages
more severe loss of limb development
what are fibroblast growth factors (FGFs)
large family of proteins that are secreted by other cells
what can FGFs mimic
the function of the AER
what can proximal-distal outgrowth be rescued by
replacing the AER with FGF-coated beads because FGF coated beads can induce supernumerary limbs
Explain model for proximal-distal axis specification
Fgf8 stimulates fgf10 and allows it to proliferate. Fgf10 stimulated fgf8 and allows it to proliferate. constant loop. Reciprocal secretion; if cut off, arrest in limb formation
what is the proximal-distal axis comprised of in the genome
hox gene clusters A-D
what is the significance of hox gene expression
hox gene expression pattern correlates with identity of elements along the proximal-distal axis
what is Hox 9 associated with
important in the development of all parts of limb
what is Hox 10 gene associated with
stylopod, zeugopod, and autopod, and phalanx
what is Hox 11 associated with
zeugopod, autopod, and phalanx
what is Hox 12 associated with
autopod and phalanx
what is Hox 13 associated with
phalanx
what does each cell have in proximal-distal patterning that tells it it’s fate
positional address
How is cell fate regulated in limb formation
positional address; varying concentration, and spacio-temporal expression patterns of signals (FGFs, Wnts) regulate cell fate specification along prox.-dist. axis
what is the significance of the Zone of Polarizing Activity (ZPA)
ZPA is sufficient for specification of posterior fate
what gene is expressed in the ZPA
sonic hedgehog (Shh)
what is needed for the formation of fingers and toes
apoptosis and bone morphogenic proteins (BMPs)
what does an increase in BMP signaling cause
increase in cell death; digits freed earlier than should be
what does a decrease in BMP signaling cause
decrease in cell death; webbed digits
what is significant about day 56 in fetal development
fingers of the right and left hand overlap along midline. This helps track fetal growth!
what occurs in limb rotation (weeks 6-8)
upper limbs laterally rotate 90 degrees
lower limbs medially rotate 90 degrees
what cells do limb muscles arise from
hypomeres (paraxial mesoderm)
what does the dorsal muscle mass form
extensors and supinators in upper limb
extensors and abductors in lower limb
what does the ventral muscle mass form
flexors and pronators of the upper limb
flexors and adductors of lower limb
where do limb tendons arise from
lateral plate mesoderm
where do bones arise from
lateral plate mesoderm
how are bones formed
- mesenchymal cells condense and differentiate into chondrocytes
- hypertrophic chondrocytes secrete VEGF
- Blood vessels invade the center bringing in osteoblasts
- osteoblasts bind mineralized matrix
- at birth, diaphysis (shaft) is completely ossified whereas the epiphysis (end of long bone) is still cartilaginous
- at birth, secondary ossification centers develop and perform 1-4 again
- layer of cartilage called epiphyseal cartilage plate (growth plate or physis) persists between epiphysis and the growing end of diaphysis
what is the significance of FGFR3
it is a negative regulator of chondrocyte proliferation
what innervates limbs
ventral ramus
what do nerve branches go through
decision making regions
what is significant about decision making regions
nerves make up mind on where they want to innervate
brachial plexus- upper limb
lumbosacral plexus- lower limb
what is the prevalence of limb defects in live births
1:200 live births
not uncommon
what are the reduction defects of limb formation
meromelia
amelia
phocomelia
adactyly
what is meromelia
absence of part of a limb
later or partial loss of AER of FGF signaling
what is amelia
absence of entire limb
early loss of AER or FGF signaling
what is phocomelia
short, poorly formed limb
partial loss of FGF signaling or Hox disruption
what caused phocomelia
thalidomide- medication
non genetic cause
what weeks are embryos most susceptible to teratogen-induced lumb malformations
weeks 4-5
what is a consequence of phocomelia
angiogenesis inhibition and altered cytokine production
what is adactyly
absence of digits
what is polydactyly
duplication defect
extra digits
what causes polydactyly
upregulation of Shh signaling
what is syndactyly
dysplasia
fusion of digits
what causes syndactyly
BMP disruption or Hox13 mutation
what causes split foot anomaly and ectrodactyly
absence of FGF8 expression
discontinuous AER
dysplasia anomaly
what congenital anomaly is amniotic band
dysplasia
what is amniotic band anomaly
adhesion between amnion and affected fetal structure
amnion membrane tears and forms around limbs
what is club foot
dysplasia
oligohydramnios- insufficient amount of fluid and space for limbs to grow
unrelated to limb rotation!
what is achondroplasia
short limb dwarfism
what inheritance pattern is achondroplasia
autosomal dominant
what causes achondroplasia
activating mutations in FGFR3, which leads to decreased chondrocyte (end of bone) proliferation = short bones
