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Histology/Embryology > EXAM2_HE18_LIMB_Development > Flashcards

EXAM2_HE18_LIMB_Development Flashcards

1
Q

What expression at primitive node initiates/maintains primitive streak?

A

Nodal (TGF-B family)

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2
Q

What expression at primitive streak controls cell migration (invagination)?

A

FGF8

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3
Q

What expression drives left/right asymmetry later in development?

A

FGF8 and Nodal expression

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4
Q 
Where developed from:
Vasculature of limbs?
long bones of limbs?
Respiratory system?
Visceral organs?
Gi system?
CT?
A

Vasculature of limbs- Lateral Plate Visceral
long bones- lateral plate Somatic
Respiratory system- lateral plate visceral
Visceral organs & GI- lateral plate visceral
CT- somatic lateral plate mesoderm

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5
Q

MYOTOME differentiation:
2 divisions. What do each form? what expression for each?

When does myotome differentiation occur?

A
  1. Hypaxial- body wall & limb muscles- anterior primary rami
    (MyoD expression-posterolateral origin of paraxial somite)
  2. Epaxial- Intrinsic back muscles- post primary rami
    (Myf5 expression)- posteromedial origin of paraxial somite)

AT 5 WEEKS!

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6
Q

Signaling for hypaxial and epaxial- what about dermis?

A

BMP4 & WNT>MYOD> body wall/limb muscles
SHH & WNT >MYF5> intrinsic back muscles

NT-3>PAX3>DERMIS

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7
Q

What is special about the epaxial derivatives? hypaxial derivatives?

A

epaxial ;Myoblasts do not migrate- form intrinsic back muscles
hypaxial- some don’t migrate- form intercostal muscles
some Migrate into the limb muscles

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8
Q

Limb buds- when formed? what type of tissue? where tissue from? location of upper/lower buds? what determined by?

A
  • Buds @ 4 weeks
  • Paddles @ 6 weeks
  • Fingers @ 8 weeks
    -cuboidal ectoderm
    -Has dermis deep to ectoderm
    -mesenchyme from somatic mesoderm form cartilage>bone
    -Upper limb bud C4-T2
    -Lower limb bud L1-S2
    Determined by HOX genes

mesenchyme>dermis>cuboidal ectoderm layers of limbs

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9
Q

What segments of top part of arm? Lower part of arm?

What segments of lateral leg? midline of leg?

A

Top surface- c4-c7
Under surface T1-T2
lateral leg- L2-L5
midline leg- s1-s3

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10
Q 
Apical Ectodermal Ridge (AER)
what causes differentiation?
what does it regulate?
what kind of cells in differentiation zone?
where derived from?
when digits formed?
A
  • AER differentiates response from FGF from mesoderm
  • Differentiation zone (chondrocytes & CT) Low FGF is proximal
  • Proliferative/progress zone Hi FGF-extends limb
  • Mesenchyme from lateral plate somatic mesoderm
  • cartilaginous digital rays form in each digit 6-8wks
  • apoptosis creates digits by 8 weeks
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11
Q

describe the FGF concentration and its role in limb development. High FGF region? low FGF region? what happens there? What it’s called?

A

Distal End of AER- HIGH FGF= progress zone (proliferative) mitotic

Proximal to AER- LOW FGF = differentiation zone

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12
Q

Nile Blue stain used for?

A

FGF

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13
Q

What is formed at 8 weeks?

6 and 4 weeks?

A

8- should have apoptosis and digits of CARTILAGE
6- paddles-Hyaline cartilage
4- buds

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14
Q

Limb development 6 weeks? 8 weeks? 12 weeks? Birth?

what limbs form faster? by how much?

A

6- limb bones exist as hyaline cartilage models
8- endochondral ossification begins in center of diaphysis
12- primary ossification centers formed
birth- diaphysis is ossified- epiphysis has active secondary ossification centers- branches of intersegmental arteries grow into developing limbs-
Upper limb develop 1-2 days before lower limbs

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15
Q

what is the flow of bone formation?

A

mesenchyme>cartilage> bv & osteoblasts arrive via blood> ossification

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16
Q

Limb Rotation- When; what rotates how much where?

A 
Begins @ 7 weeks
-Upper limb rotates 90deg laterally
extensors posterior-thumb lateral
flexors anterior
thumb lateral

-Lower limb rotates 90deg medially
extensors anterior
flexors posterior
big toe medial

17
Q

Limb muscle formation and innervation.

A
  • Skeletal myoblasts from HYPAXIAL division of myotome migrate into limb bud by 7 weeks
  • CT in the limbs guides myoblast formation of skeletal muscle
18
Q

problem with CT during limb formation?

A

if there is a problem with the CT during limb formation the myoblasts will not be patterned correctly

19
Q

SOMATIC vs SOMITIC

A

Somatic - referring to lateral plate somatic mesoderm

Somitic- referring to paraxial plate mesoderm somites

20
Q

What controls the patterns of muscle formation in the limbs? Why is this so important?

Where are occipital/cervical myoblasts derived from?
Where are Body wall/ Limb myoblasts derived from?

A

CT Fibroblasts (somatic lateral plate)- in buds will direct the myoblasts migration and massing

-Myoblasts migrate within CT in limb buds and develop into specific muscle divisions

Occipital/Cervical muscles- from SOMITIC mesoderm of paraxial mesoderm

Body wall/limbs- SOMATIC mesoderm from lateral plate mesoderm

21
Q

Where can Connective tissue be derived from?

Head, Cervical/Occipital, Limbs.

A

Lateral Plate- somatic MAINLY- limb ct for myo formation
Paraxial mesoderm- cervical/occipital ct for myo formation
Neural crest- CT for myo formation of head muscles

22
Q

Innervation of muscles- What RAMI? 2 divisions of that rami? Functions of each division?

Why is nerve/muscle contact so important?

A

ANTERIOR PRIMARY RAMI forms appropriate spinal nerves that enter limb buds and has TWO DIVISIONS:

  1. Anterior division- innervates flexors of limbs
  2. Posterior division- innervates extensors of limbs

nerve/muscle contact required for complete differentiation
-if muscle develops without innervation- they malfunction

23
Q

What nerves innervate extensor muscles of the arm and forearm?

A

Posterior division of the ANTERIOR PRIMARY RAMI forms a posterior nerve:
1. RADIAL NERVE- extensor muscles of the arm and forearm

24
Q

What nerves innervate Flexor muscles of the arm? flexor muscles of the forearm?

A

Anterior division of the ANTERIOR PRIMARY RAMI forms 3 anterior nerves:

  1. MUSCULOCUTANEOUS NERVE- flexor muscles of ARM
  2. ULNAR & MEDIAN NERVES- flexors of FOREARM
25
Q

Clinical aspects of limb development- AER/ZPA
What is AER- where derived from? what expressed? why?
What is ZPA- where derived from? what expressed? why?

What affects proper limb growth/digit order/ etc?

A

AER- apical ectodermal ridge expresses FGF to maintain progress zone.
ZPA- zone of polarizing activity derived from mesoderm
-located posterior margin of limb bud- expresses SSH (sonic hedgehog).
-SSH controls anterior-posterior patterning
AER + ZPA req. for proper limb bud outgrowth, digit order, etc.

26
Q

Where does ZPA form? why is this important? What is expressed? what gradient?

A

ZPA forms anterior/posterior axis

  • forms initially on posterior side of limb and produces SSH.
  • SSH gradient higher posterior and less SSH anterior
27
Q

What determines the final length and size of limb?

What happens if you remove SHH from AER?

A

Breakdown feedback between AER (FGF) and ZPA (SHH)-

-ectopic digit formed if SHH removed from AER (SHH removed from ectoderm not from mesoderm).

28
Q

How does AER and ZPA regulate signaling and limb development?

A

Feedback loop between AER/ZPA establishes proper amount of SHH and FGF for limb development

29
Q

If you take out SHH of ectoderm only?
If SHH removed completely?
How does morphology fingers relate to SHH?

A

extra digit if SHH removed from ectoderm
only thumb develops if SHH removed entirely
-thumb is independent of SHH:

  • SHH Gradient (HIGH pinky 5, 4, 3, 2 LOW)
  • NO SHH creates the thumb
30
Q

AER/ZPA- ZPA transplanted to ANTERIOR margin of limb bud. What was result?

A

Limb developed with TWO POSTERIOR IDENTITIES

  • No thumbs developed
  • Fingers 5,4,3,3,4,5 with no 1 or 2 digits
31
Q

Patterns of limb development:
Ablation of FORELIMB PARAXIAL MESODERM:
Ablation of TRUNK PARAXIAL MESODERM:
Why is this experiment important?

A

Forelimb ablation- decreases limb bud outgrowth
Trunk ablation- increases limb bud outgrowth

  • Limb buds form from somatic lateral plate mesoderm
  • -Important discovery that a relationship exists between Paraxial mesoderm (seemingly unrelated to limb bud growth) and limb bud growth.
32
Q

3 experiments done to confirm relationship of paraxial mesoderm to limb development

What was result of Last experiment?

A
  1. ablation of forelimb/trunk paraxial mesoderm
  2. Counted cell proliferation resulting from ablation
  3. transplant excess forelimb/trunk paraxial mesoderm

Extra forelimb mesoderm> bigger growth
Extra trunk mesoderm> smaller growth

33
Q

OVERALL results of experiments for limb bud development?

A

Forelimb Paraxial mesoderm stimulates limb growth

Trunk paraxial mesoderm inhibits limb growth

34
Q

What genes regulate morphology? How many do we have?

A
  • Humans have 4 sets of HOX genes

- HOX genes regulate types and shapes of bones (morphology)

35
Q

4 Digital Defects:

A
  1. brachydactyly- short digits
  2. Polydactyly- extra digits
  3. Syndactyly- fused digits
  4. Cleft foot- extreme syndactyly (all merged to 2 digits)
36
Q

Signaling factors in limb development- what does each regulate?
GDF5
Scleraxis
BMP4

A

GDF5- where joints will form
Scleraxis- future tendons
BMP4- areas apoptosis

Histology/Embryology (8 decks)

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