Embryo Limb Development Flashcards by Megan Lidtke

where do the muscles of the limbs arise from?

Paraxial mesoderm

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where do the limbs arise from?

somatic mesoderm

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what weeks do the limbs form in

weeks 4-8

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when are the basic structures of limbs (bones and muscle groups) established

between weeks 4-8

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when do the fingers separate and ossification begins?

day 56

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what germ layer does the limb bud come from

ectoderm and lateral plate (somatic) mesoderm

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what germ layer do the bones, tendons, and vasculature come from

lateral plate (somatic) mesoderm

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what germ layer do the muscles come from

paraxial mesoderm

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when does the upper limb bud form

day 24

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when does the lower limb bud form

day 28

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what are the 3 axes of limb bud formation

proximal-distal
cranial-caudal
dorsal-ventral

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what is proximal-distal growth controlled by

Apical ectodermal ridge (AER)

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what is the AER necessary for

limb outgrowth

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what is the AER sufficient for

Limb outgrowth

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what is significant about removal of the AER at later stages

loss in more distal elements, less severe

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what is significant about removal of the AER at earlier stages

more severe loss of limb development

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what are fibroblast growth factors (FGFs)

large family of proteins that are secreted by other cells

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what can FGFs mimic

the function of the AER

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what can proximal-distal outgrowth be rescued by

replacing the AER with FGF-coated beads because FGF coated beads can induce supernumerary limbs

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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

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what is the proximal-distal axis comprised of in the genome

hox gene clusters A-D

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what is the significance of hox gene expression

hox gene expression pattern correlates with identity of elements along the proximal-distal axis

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what is Hox 9 associated with

important in the development of all parts of limb

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what is Hox 10 gene associated with

stylopod, zeugopod, and autopod, and phalanx

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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

1. mesenchymal cells condense and differentiate into chondrocytes 2. hypertrophic chondrocytes secrete VEGF 3. Blood vessels invade the center bringing in osteoblasts 4. osteoblasts bind mineralized matrix 5. at birth, diaphysis (shaft) is completely ossified whereas the epiphysis (end of long bone) is still cartilaginous 6. at birth, secondary ossification centers develop and perform 1-4 again 7. 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