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ANAT 400 - Embryology > Limb development > Flashcards

Limb development Flashcards

1
Q

Each limb bud has an external layer of ______ and a core of ______ Muscle and tendon cells originate in the _____ and later migrate into the limb bud

A

Each limb bud has an external layer of ectoderm and a core of somatic (lateral plate) mesoderm Muscle and tendon cells originate in the somite and later migrate into the limb bud

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2
Q

Muscles and tendons of the limbs come from _______

A

Muscles and tendons of the limbs come from myoblasts (somites)

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3
Q

Bones, connective tissue (fascia), dermis of the limbs comes from _______

A

Bones, connective tissue (fascia), dermis of the limbs comes from somatic lateral plate mesoderm (all connective tissue of limb bud)

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4
Q

What is the Apical Ectodermal Ridge (AER)?

What induces its formation?

What factor is expressed in the AER

A
  • APICAL ECTODERMAL RIDGE (AER)
    • A distinct ridge of ectoderm at the distal end of the limb bud
    • Signals in the underlying somatic mesoderm induce formation of the AER
    • AER express fibroblast growth factor 8 (FGF8)
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5
Q

Limb buds grow from _______ axis

  • ____ maintains the cells behind the AER in a proliferative, undifferentiated state
  • As the AER extends further _____, some cells escape the _____ signal and start to differentiate
  • Thus, the AER drives growth of the limb bud along the _______ axis
A

Limb buds grow from proximal to distal axis

  • FGF8 maintains the cells behind the AER in a proliferative, undifferentiated state
  • As the AER extends further distally, some cells escape the FGF8 signal and start to differentiate
  • Thus, the AER drives growth of the limb bud along the proximal-distal axis
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6
Q

As limbs grow they are patterned along 3 axes:

  • ________ (eg shoulder to fingertips)
  • _______ (eg thumb to pinky)
  • ______ (eg back of hand vs palm)
A

As limbs grow they are patterned along 3 axes:

  • proximal-distal (eg shoulder to fingertips)
  • cranial-caudal (eg thumb to pinky)
  • dorsal-ventral (eg back of hand vs palm)
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7
Q

What are the three parts that the limb is separated into in the Proximal-distal axis?

A
  • Stylopod
  • Zeugopod
  • Autopod
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8
Q

What are the three parts that the limb is separated into in the Proximal-distal axis?

A
  • Stylopod
  • Zeugopod
  • Autopod
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9
Q

Proximal-distal axis

  • What controls the order of differentiation
  • What do we pattern first?
A

Proximal-distal axis

  • What controls the order of differentiation
    • AER (apical ectodermal ridge)
    • Halted growth by cutting AER at various stages
  • What do we pattern first?
    • Sylopod
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10
Q

Proximal-distal axis:

-How do the differentiating cells know what to become?

A
  • Each region of the limb expresses a different Hox gene code, leading to formation of different structures along the P-D axis
  • Hox gene mutations lead to missing segments
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11
Q

What is the timing model of proximal-distal limb patterning?

A
  • Temporal differentiation
  • Cells know the order in which they are differentiating (eg count cell divisions and know what to become based on their cell division number)
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12
Q

What is the morphogen model of proximal-distal limb patterning

A
  • FGFs (fibroblast growth factors) in the AER and Retinoic acid in the flank form two opposing morphogen gradients along the proximal-distal axis
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13
Q

Both morphogen gradients and timing mechanism are needed to pattern entire P-D axis:

  • _______ pattern stylopod/zeugopod
  • _______ patterns autopod
A

Both morphogen gradients and timing mechanism are needed to pattern entire P-D axis:

  • morphogens pattern stylopod/zeugopod
  • timing mechanisms patterns autopod
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14
Q

Morphogens in the _______ pattern the dorsal-ventral axis of the limb

A

Morphogens in the overlying ectoderm (developing skin) pattern the dorsal-ventral axis of the limb

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15
Q

Cranial Caudal axis:

  • A ________ in the caudal limb bud patterns the cranial-caudal axis
  • _______ is expressed by cells in [this region]
  • As ____ is secreted, a gradient forms (____ caudal, ___ cranial) to pattern the axis
A

Cranial Caudal axis:

  • A zone of polarizing activity in the caudal limb bud patterns the cranial-caudal axis
  • Sonic hedgehog is expressed by cells in the ZPA
  • As SHH is secreted, a gradient forms (high caudal, low cranial) to pattern the axis
    • ie thumb forms where SHH is lowest (cranial)
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16
Q

How was the ZPA discovered?

A

Zone of Polarizing Activity

  • Transplant of the zone of polarizing activity (ZPA) from a donor onto the cranial margin of the wing bud of host induced a mirror duplication of the cranial-caudal axis
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17
Q

How are individual bones established?

A
  • Turing reaction-diffusion mechanism
    • uses 2 or more interacting molecules that sort themselves into a more complex pattern
    • Need both an ACTIVATOR that activates BOTH ITSELF and AN INHIBITOR
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18
Q

What is the Turing reaction-diffusion mechanism?

A
  • Turing reaction-diffusion mechanism
    • uses 2 or more interacting molecules that sort themselves into a more complex pattern
    • Need both an ACTIVATOR that activates BOTH ITSELF and AN INHIBITOR
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19
Q

What 3 signaling molecules interact to create individual digits (via turing reaction-diffusion mechanism)?

Which of these drives cartilage formation?

A
  • Wnt
  • Bmp
  • Sox9
  • Create a repeating stripe of Sox9 which will start to form cartilage
20
Q

What separates the digits?

A

Apoptosis

21
Q

How (and when) are the limb bones formed?

  • 5th-6th weeks: _______ condensations form from ________
  • 6th-8th weeks: _______ (cartilage models form for each bone)
  • 7th-12th weeks: ________ in most limb bones
    • A few don’t appear until after birth
A
  • 5th-6th weeks: Mesenchymal condensations form from somatic lateral plate mesoderm
  • 6th-8th weeks: Chondrification (cartilage models form for each bone)
  • 7th-12th weeks: Ossification centers appear in most limb bones
    • A few don’t appear until after birth
22
Q

What are the stages of chondrocyte development?

When do they occur?

A

Quiescent → proliferation → hypertrophy → death and replacement by osteoblasts

Occur during initial bone formation and at the growth plate

23
Q

During each step in development, the chondrocytes express a different set of ______

A

During each step in development, the chondrocytes express a different set of genes

  • Mutation in any of these genes depends on the particular role for that gene in bone development
    • eg can cause reduced chondrocyte proliferation, premature hypertrophy, reduced differentiation
23
Q

During each step in development, the chondrocytes express a different set of ______

A

During each step in development, the chondrocytes express a different set of genes

  • Mutation in any of these genes depends on the particular role for that gene in bone development
    • eg can cause reduced chondrocyte proliferation, premature hypertrophy, reduced differentiation
24
Q

What are bony eminences and how are they formed?

What is expressed in bone eminences?

A
  • Bone eminences = bumps for attachment of ligaments and tendons
    • specifically pattered during development but form secondary to the main bone
    • Scleraxis is expressed in tendons and ligaments but also in bone eminences
      • Creates a Transition Zone between bone and tendon/ligament
25
Q
  • _____ is expressed in tendons and ligaments but also in bone eminences
    • Creates a Transition Zone between bone and tendon/ligament
A
  • Scleraxis is expressed in tendons and ligaments but also in bone eminences
    • Creates a Transition Zone between bone and tendon/ligament
26
Q

How are joints created?

A

Mesenchyme of future joint

  • (+chondrogenesis)*↓ | ↓(- chondrogenesis)
  • Articular Cartilage* | Synovial cavity, ligaments, capsule
  • Need to both promote and inhibit chondrogenesis
27
Q

What transcription factor promotes formation of articular cartilage?

A

Gdf5

28
Q

Cavitation to form the synovial cavity is achieved by the secretion of ______

A

Cavitation to form the synovial cavity is achieved by the secretion of hyaluronic acid

  • glycosaminoglycan that readily absorbs water - thereby creating tissue spaces (draws fluid in to create jelly-filled cavity)
29
Q

What promotes hyaluronic acid synthesis required for cavitation to form the synovial cavity

A

In utero movements

30
Q

Limb musculature originates from ______ at the _____ edge of the _______

A

Limb musculature originates from myoblasts at the ventrolateral edge of the myotome

31
Q
  • As myoblasts migrate into the limb bud they are ______
  • Become specified as limb muscles by ______
  • Divide into dorsal and ventral masses which from the _____ and _____ respectfully
A
  • As myoblasts migrate into the limb bud they are proliferating
  • Become specified as limb muscles by mesenchyme (somatic mesoderm)
  • Divide into dorsal and ventral masses which from the extensors and flexors respectfully
32
Q

Dorsal-ventral muscle patterning comes from _____

A

Dorsal-ventral muscle patterning comes from overlying ectoderm

33
Q

Movement and refinement:

  • Excess muscle fibers (each fiber is a _______) are made initially and then undergo ______. The formation of new fibers ends around birth.
  • Postnatal growth is through fusion of ________ with existing ________.
  • Embryonic movements are important for development of the musculoskeletal system. For example, the proper _______, alignment of _____, growth of ______, development of ______
  • Spontaneous movements start as early as _______
A
  • Excess muscle fibers (each fiber is a single, multi- nucleated cell) are made initially and then undergo apoptosis. Formation of new fibers ends around birth.
  • Postnatal growth is through fusion of progenitor cells with existing muscle fibers.
  • Embryonic movements are important for development of the musculoskeletal system. For example, the proper attachment of tendons, alignment of bones, growth of muscles, development of joints
  • Spontaneous movements start as early as 7 weeks.
34
Q

Limbs are innervated by motor nerves from the ______ and sensory nerves from _______

  • _______ plexus = C5-T1
  • _______ plexus = L4-S3
A

Limbs are innervated by motor nerves from the ventral spinal cord and sensory nerves from adjacent dorsal root ganglia

  • branchial plexus = C5-T1
  • lumbosacral plexus = L4-S3
35
Q

Motor neuron sorting:

Axons that travel into the dorsal side of the limb innervate _____ muscles

Axons that travel into the ventral part of the limb innervate ____ muscles

A

Axons that travel into the dorsal side of the limb innervate extensor muscles

Axons that travel into the ventral part of the limb innervate flexor muscles

36
Q
  • Motor neurons from the _____ project to axial and body wall muscles
  • Motor neurons of the _____ project to the limb
  • The ______ innervates the dorsal limb
  • The _____ innervates the ventral limb
A
  • Motor neurons from the MMC (medial motor column) project to axial and body wall muscles
  • Motor neurons of the LMC (lateral motor column) project to the limb
  • The Lateral pool of the LMC (LMCl) innervates the dorsal limb
  • The Medial pool of the LMC (LMCm) innervates the ventral limb
37
Q

The final step of limb development is Limb Rotation.

  • Limb buds initially point _____ and _____
  • After joint is added, limbs ______
    • Elbow and knew point ______
A
  • Limb buds initially point laterally and caudally
  • After joint is added, limbs flex ventrally
    • Elbow and knew point laterally
38
Q

Limb rotation in the 8th week:

  • Arms rotate ______ so that the ventral (____) surface faces _____
  • Legs rotate ______ so that the dorsal (_____) surfaces faces _______
  • Elbows now point _____ when flexed
  • Knees now point ____ when flexed
A

Limb rotation in the 8th week:

  • Arms rotate 90° laterally so that the ventral (flexor) surface faces anteriorly
  • Legs rotate 90° medially so that the dorsal (extensor) surfaces faces anteriorly
  • Elbows now point caudally when flexed
  • Knees now point cranially when flexed
39
Q

Label the 4 congenital limb anomalies

A
40
Q

Different ways in which limb development may go wrong, perhaps related to ______ patterning

Common defects: (4)

A

Different ways in which limb development may go wrong, perhaps related to Hox gene patterning

Common defects: (4)

  • absence or partial absence of a limb
  • over or undergrowth of limb
  • duplications
  • failed separation (eg fused fingers)
41
Q

What kinds of anomalies arise if there is defect in the genes involved in chondrocyte steps?

A

Skeletal malformations

42
Q

What are some environmental causes of limb anomalies?

A
  • Anything that compromises blood supply (eg causes vasoconstriction)
    • warfarin
    • thalidomide
    • phenytoin
    • valproic acid
    • cocaine
    • sugar (ie maternal diabetes)
    • infections
43
Q

What are possible physical restraints on growth?

A
  • Amniotic band constriction
  • Oligohydramnios
    • low amniotic fluid
    • impair movement that is important for limb development
44
Q

What is Club foot?

A
  • more common anomalies
  • Foot twisted out of shape an/or position
  • Bone and soft tissue abnormalities (eg short tendons, underdeveloped calf muscles
    • difficult to correct

ANAT 400 - Embryology (14 decks)

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