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Anatomy ICOM > Limb Development > Flashcards

Limb Development Flashcards

1
Q

Limb primordia

A
  1. Mesoderm
    A. Paraxial: somites -> muscles only
    B. Lateral plate: somatic mesoderm -> mesenchyme-> cartilage -> bone, CT, blood vessels
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2
Q

Nerve primordia

A
  1. Ectoderm
    A. Neural crest: afferent innervation and myelination
    B. Neural tube: efferent innervation
    *sympathetics and parasympathetics
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3
Q

AER (apical ectodermal ridge)

A

Ridge of ectoderm along cranial/caudal axis where limb buds form

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4
Q

ZPA (zone of polarizing activity)

A

Forms at caudal end of limb bud

1. Creates SHH gradient

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5
Q

FGF (fibroblast growth factors)

A

FGF10 -> AER secretes FGF8 -> ZPA

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6
Q

SHH (sonic hedgehog)

A

Primary growth factor

1. Gradient defines anterior/posterior limb pattern

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7
Q

BMP (bone morphogenic protein)

A
  1. Expressed by ventral ectoderm
  2. BMP -> EN1 to set up dorsal/ventral gradient
  3. Helps -> AER via FGF10
  4. Vital for finger differentiation
    A. Apoptosis in webbing
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8
Q

HOX (homeobox domain genes)

A
  1. HOXa and HOXd = primary determinants of bone morphology

2. HOXD 9-13 expression based on A/P and P/D concentration gradients of SHH, FGFs, and WNT7a

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9
Q

WNT7a

A

Dorsal limb ectoderm

  1. Establishes dorsal/ventral gradient
  2. Interacts w/ AER-FGF -> SHH
  3. Maintain proximal/distal axis by maintaining mesenchyme along AER
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10
Q

EN1 (entrained 1)

A

Stimulated be BMP in ventral limb

1. Suppresses WNT7a ventrally => WNT7a dorsal/ventral gradient

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11
Q

Abnormal limb development

A
  1. Change in regulation of primary players -> cascade effect
  2. Environmental factors: teratogens during let dev. Periods
    A. Alcohol
    B. Thalidomide
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12
Q

Axes of growth

A
  1. Ant/post -> lat/medial
  2. Prox/distal
  3. Dorsal/ventral -> post/ant
    * starts ant/post like quadruped
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13
Q

Anterior/posterior gradient formation

A

3 weeks
1. Growth initiates as bud forms
A. FGF10 from mesenchyme -> AER forms outgrowth in ectoderm
B. Cells of AER
1. Stimulate FGF8 -> distal growth
2. Stimulate ZPA form at post aspect-> ant/post gradient
C. ZPA releases SHH -> ant/post gradient
1. SHH gradient dictated bone formation
A. Thumb and radius- low/absent [SHH]
B. 2nd and 3rd digits - med [SHH]
C. 4th and 5th digits and ulna - high [SHH]

  1. Cross-sections
    A. Zeugopod- arm (radius/ulna)
    B. Autopod - hand
    C. Stylopod- humerus
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14
Q

Amelia

A

Absence of limbs
1. Suppression of limb bud dev. During 4th week
A. No ZPA

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15
Q

Polydactyly

A

Extra fingers
1. Cause: error in SHH transcription w/in limb buds -> A/P gradient mutations

  1. Pre-axial: 2 thumbs
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16
Q

Bradydactyly

A

Short terminal phalanges

1. Cause: HOXD 9-13 mutation

17
Q

Digit formation

A
  1. Phalanx forming region stim interdigital mesenchyme to differentiate according to pre/post axial gradient
  2. Based on SHH signaling
  3. Mediated by BMP
  4. Weeks 4-8
    A. Limb buds
    B. Paddle-shaped hand and footplates
    C. Digital rays
    D. Notched between digital rays
    E. Webbed fingers/toes
    F. Separate digits
18
Q

Syndactyly

A 
Webbing
1. Incomplete formation of interdigital clefts
2. Cause: lack apoptosis between digits
  A. Usually BMP mutations
  B. Can involve SHH mutation
19
Q

Proximal/distal gradient

A
  1. Differentiation front model
    A. PZ (proliferating zone) - undifferentiated front along AER
    B. AER produces FGF8 -> mesenchymal cell division in PZ
    C. PZ differentiates according to distal distance traveled
    D. PZ position relative to AER determines HOXD gene expression => prox/distal tissue density
    E. HOXD9-13 control tissue ID beyond differentiation front
20
Q

Meromelia

A

Partial absence of limbs
1. Terminal: missing hands
2. Intercalary: missing parts
A. Phocomelia: hands present, prox parts missing
B. Hemimelia: missing at least one zeugopod bone (radius/ulna)
3. Cause: disruption of prox/distal dev. In 5th week
A. Variable mutations
B. Mostly HOXD mutations

21
Q

Dorsal/ventral gradient

A

As limb bud elongates

  1. WNT7a in dorsal ectoderm
  2. EN1 in ventral ectoderm
  3. EN1 inhibits WNT7a ventrally => WNT7a dorsal/ventral gradient
  4. Mesenchyme differentiates ant/post limb compartments
22
Q

Limb rotation

A 
7-8 weeks
1. Upper limb rotates 90 degrees laterally ->
  A. Elbow point post
  B. All extensors post
  C. All flexors ant
2. Lower limb rotates 90 degrees medially->
  A. Knee point ant
  B. Leg and foot flexors post
  C. Extensors ant
23
Q

Bone development

A
  1. Not scleratomes of somites bc appendicular, not axial
  2. Endochondral ossification
    A. Week 5: mesenchymal models made from lateral plate mesoderm
    B. Week 6: mesenchymal tissue in hand plates condense -> cartilaginous digital rays
    C. Week 7: start ossification long bones
    1. Ossification centers in all long bones 12th week
    2. Carpals don’t ossify until after birth
24
Q

Fusion of epiphyses

A
  1. Growth plates between epiphyses and diaphyses
  2. Happens at different time depending on location
  3. Most fuse by 18-20 y/o
25
Q

Dwarfism

A
  1. Hypochondroplasia
  2. Achondroplasia
  3. Chondrodysplasia
  4. Cause: FGF3 mutation -> problems w/ collagen production or turning collagen to bone
  5. Epiphyses and diaphyses fuse early or fail to fuse
26
Q

Muscle development

A
  1. Week 5: ventral rami invade limb buds carrying myoblasts from C5-T1 somites in upper limb
    A. L2-S3 somites in lower limb
  2. Myocytes aggregate and proliferate -> ventral/dorsal muscle mass
  3. Mesenchyme from lateral plate mesoderm -> ligaments and blood vessels
  4. Mytotomes: set of muscles innervation by specific spinal n.
    A. Muscle mass from each myotome porliferated into limb prox -> distal
    B. Overlap from migration/fusion of myotomes
27
Q

Dermatome development

A

Sensory axons enter limb bud after motor axons from neural crest
1. Sensory nerves envelope in epidermis and pulled along ventral axis pre -> post axial

Anatomy ICOM (34 decks)

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