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SPOM > Limb Development > Flashcards

Limb Development Flashcards

1
Q

When does the limb start to develop?

A

around 4-8 weeks

-4 weeks: limb bud

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2
Q

Which limb develops first?

A
  • fore limb

- hind limb 1 to 2 days later

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3
Q

Limb development is an interaction between what?

A

Epithelial-Mesenchymal interaction:

  • Ectoderm
  • Mesoderm
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4
Q

What do limbs arise from?

A

Lateral Plate Mesoderm

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5
Q

Where does the limb know where to start development on the embryo?

A
  • competent stripe

- HOX genes are expressed along the competent stripe at the point where limbs develop

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6
Q

What initiates and maintains bud outgrowth?

A
  • by establishing a positive feedback loop of FGF signaling comprised of FGF10 expressed in the Lateral Plate Mesoderm
  • controlled by Tbx transcription factors
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7
Q

What transcription factors control the formation of forelimb? Hindlimb?

A

Forelimb: Tbx5

Hindlimb: Tbx4

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8
Q

What is the ultimate signal for initiation of limb outgrowth?

A

Wnt-3

Sources of signal:

  • Paraxial (somatic) Mesoderm
  • Intermediate Mesoderm
  • HOX determines where
  • Wnt determines when, regulates Tbx
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9
Q

Amelia? Defective signal?

A
  • failed development of one or more limbs, could be shrunken or deformed
  • Meromelia: partial absence of limbs
  • Tetra-amelia: failure of all 4 limbs
  • linked to defect in Wnt3 signaling
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10
Q

Apical Ectodermal Ridge (AER)?

A
  • condensation of ectodermal cells
  • creates a proliferative zone beneath, called the progress zone (0.4mm thick)
  • border between dorsal and ventral
  • gradient in either direction, differentiates the two
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11
Q

What transcription factors are expressed in the Apical Ectodermal Ridge (AER)?

A
  • Dorsal ectoderm: Wnt-7a

- Ventral ectoderm: Engrailed-1

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12
Q

What happens when the AER is removed?

A
  • removal results in loss of limb element
  • remove early: lose radius, ulna, and hand
  • remove late: lose hand
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13
Q

Diplopodia?

A
  • congenital anomaly in tetrapods that involves duplication of elements of the foot on the hind limb
  • duplication of AER result in supernumerary limbs
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14
Q

Zone of polarizing activity (ZPA)?

A
  • found at distal (posterior) base of limb bud
  • produces anterior and posterior limb pattern
  • secretes sonic hedge hog (shh)
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15
Q

Acheiropodia?

A
  • autosomal recessive developmental disorder presenting with bilateral congenital amputations of upper and lower extremities and aplasia of hands and feet (hemimelia)
  • lack of shh
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16
Q

Polydactyly? post and preaxial?

A
  • congenital physical anomaly in humans and animals having supernumerary fingers or toes
  • opposite of oligodactyly (fewer fingers and toes)
  • Preaxial: result from ZPA duplication (duplication of 1st or 2nd digit)
  • Postaxial: addition of another digit (6th digit)
17
Q

Tetrapod body plan?

A
  • stylopod: humerus
  • zeugopod: ulna and radius, tibia and fibula
  • autopod: wrist and fingers, ankle and toes
18
Q

Progress zone model of proximal-distal axis patterning?

A
  • mesoderm at the distal tip of the limb bud constitutes a progress zone of fixed dimensions, in which cells are receiving progressively more distal positional information over time
  • new layers formed in succession
  • first PZ, then stylopod, then S and Z; then S,Z and A
19
Q

Early specification model of proximo-distal axis patterning?

A
  • early limb bud stage, cells are broadly specified to for the three compartments of the limb, the cells undergo expansion before becoming determined to form different skeletal elements
  • all layers (S, Z, A) are present from the beginning, but grow and differentiate
20
Q

Cartilage condensation process?

A
  1. cells exit progress zone
  2. condense or aggregate
  3. differentiate into chondrocytes
  4. becomes Cartilaginous Anlage
  5. Chondrocytes respell
  6. Interior: differentiated Cartilage
  7. Exterior: flatted cells Perichondrium
21
Q

Which limbs develops first?

A
  • forelimb first (arm)

- develops from top down

22
Q

What process defines the digits?

A

Interdigital apoptosis

23
Q

Syndacyly?

A
  • caused by failure of interdigital apoptosis

- two or more digits are fused together

24
Q

Joint formation process?

A
  1. cartilage condensation divided by interzones
  2. Articular cartilage differentiates
  3. Joint cavity forms (anlage)
25
Q

Bone and cartilage development process?

A
  1. Bone collar stage: cartilage cells undergo hypertrophy
  2. Periosteal invasion: periosteum penetrates interior part of bone and replaces cartilage, osteoblast put down mineralized matrix
  3. Primary Ossification Center
  4. Creation of Epiphyseal Growth Plate
  5. Secondary Ossification Center
    - Epiphyses
    - Apophyses (trochanter)
26
Q

Layers of Growth plate?

A
  1. Resting Cartilage (stem cells)
  2. Proliferative zone (stacks)
  3. Hypertrophic zone (bigger chondrocytes)
  4. Calcification zone (replace cartilage with bone)
  5. Ossification zone
    - grow at fast rate
27
Q

How many growth plates start to fuse between ages 14-20?

A

12-15

-stop growing taller once long bones fuse

28
Q

Brachydactyly?

A
  • abnormal shortening of fingers and toes

- caused by dysfunction or premature closure of growth plate of fingers and toes

29
Q

What forms muscle development?

A
  • Myoblasts (PAX3 positive cells) migrate from dermomyotome into limb bud and enlarge
  • several myoblasts fuse to form a Myotube, which matures into skeletal muscle fiber
  • form Dorsal (dmm) and ventral (vmm) muscle masses
30
Q

Development of Ligaments and Tendons? Gene precursor?

A
  • Scx expressing cells (tendon precursors) arise from sclerotome
  • Scx expression (tendon induction) depends on ectoderm, also skeletal condensations
31
Q

Ligaments and tendons development process?

A
  1. Scx expressing tendon progenitors differentiate within limb by FGF signaling
    - TGF beta plays a role
  2. tendon progenitors organize between skeletal and muscular tissues
    - most tendons depend on presence of muscles to form (extensor and flexor tendons on hand form independent of muscle)
  3. tendon cells signal ridge formation in skeletal tissues
    - muscle contraction dictates ridge robusticity
32
Q

Vascular invasion?

A
  1. endothelial cells recruited (from local mesenchyme and somites)
  2. vasculogenesis: vessels form de novo in embryonic mesenchyme
  3. angiogenesis: primitive vessels remodeled to form adult networks
  4. regression (loss of signals) occurs at site of cartilage condensation
33
Q

Nerve invasion?

A
  1. innervation is targeted
  2. innervation pattern dictated by local pattern signals
  3. correlation between craniocaudal location of neurons and anteroposterior pattern of muscle innervation
34
Q

Limb rotation and dermatome formation?

A
  1. initially point caudally
  2. grow at right angle to body
  3. elbow and knee point outward
  4. palm and sole toward trunk
  5. lower limb: rotates cranially significantly
  6. upper limb: rotates caudally

Bone homologies:

  • radius: tibia
  • fibula: ulna

SPOM (17 decks)

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