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Medicine 2 Week 6 - 11 > Embryology of Limbs > Flashcards

Embryology of Limbs Flashcards

1
Q

From what part of the embryo do somites arise

A

Paraxial Mesoderm

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2
Q

From what part(s) of the embryo do limbs arise

A

Somites and Lateral Plate Mesoderm

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3
Q

Discuss the role of paraxial mesoderm in limb formation

A

Dermatome gives rise to dermis connective tissue

Mytotome gives rise to limb muscles

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4
Q

Discuss the role of lateral plate mesoderm in limb formation

A

Bones of upper & lower limbs

Blood Vessels

Connective tissue (except for that of the dermis) (e.g. Ligaments, Tendons, etc.)

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5
Q

Limb Bud

A

Very first limb precursor formed in an embryo

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6
Q

When do limb buds form in an embryo

A

Week 4

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7
Q

Early embryonic development progression of limbs

A

A - 5 Weeks
B - 6
C - 7

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8
Q

What is the main development in limbs after 8 weeks

A

The limb elements just increase in size

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9
Q

Lag between upper and lower limb

A

Lower limb development lags behind upper limb development by 1 to 2 days

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10
Q

How are limbs initially formed

A

Firstly as a cartilagenous model

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11
Q

Discuss the osteological development of Lower Limb growth from weeks 6 to 8

A

At first it is cartilage, with bones starting to fill in at 6 weeks

Then the bones lengthen and others continue to form

Finally by 8 weeks all the major bones have formed

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12
Q

Which bones/bone groups of the lower limb are formed at 6 weeks in an embryo

A

Pelvis, Thigh/Legs, Footplate cartilages

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13
Q

Which bones/bone groups of the lower limb are formed at 7 weeks in an embryo

A

Tarsal Cartilages

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14
Q

Which bones/bone groups of the lower limb are formed at 8 weeks in an embryo

A

Metatarsal Cartilages

Ischium

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15
Q

What are the toes like at 7 weeks

A

Still connected and not formed as individual structures

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16
Q

Rostral/Caudal

A

Rostral is the Axis situated towards the head embryologically

Caudal is the Axis situated towards the ‘tail’ embryologically

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17
Q

Relevant axes in the embryological development of a limb

A

Proximal - Distal

Anterior (Rostral) - Posterior (Caudal)

Dorsal - Ventral

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18
Q

What part of the embryo initiates limb outgrowth in the proximal-distal axis

A

The Apical Ectodermal Ridge at the tip of the limb buds

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19
Q

What direction of growth is the Apical Ectodermal Ridge (AER) responsible for

A

Proximo-distal growth

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20
Q

Effect of AER on mesenchyme

A

Causes proliferation of cartilage from mesenchyme

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21
Q

HOX Genes

A

Homeobox Genes

Group of related genes that specify regions of the body plan of an embryo

HOX Proteins encode & specify the characteristics of ‘position’

Depending on which HOX genes is expressed, difference elements will form

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22
Q

AER vs HOX Genes

A

HOX genes determines the specific components/bones that form while the AER is responsible for the lengthening/differentiation of the axis as a whole

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23
Q

Result of Disruption of HOX Genes

A

Loss of Specific Limb Elements

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24
Q

Potential causes of HOX Gene disruption

A

Mutation, Teratogens like retinoic acid/ethanol

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25
Q

What parts of the embryo initiates Dorso-Ventral Patterning of the limbs

A

WNT7 is expressed on the Dorsal Surface

ENGRAILED-1 and Bone Morphogenic Protein are expressed on the Ventral surface

26
Q

Relation of Dorso-Ventral Patterning with Proximo-Distal Outgrowth; and relevance

A

Actors of Dorso-Ventral patterning are also responsible in some part of proximo-distal outgrowth as they help set up the AER

Disruptions in D-V signals can therefore also affect proximo-distal growth as well

27
Q

What part of the embryo initiates Anterior-Posterior Limb Patterning

A

AP Patterning is initiated by the zone of polarising activity (ZPA)

It secretes an entity called sonic hedgehog which specifies the formation of posterior elements (Little Fingers)

There is a gradation of how much signalling there is across the limb from the ZPA

28
Q

Results of loss/upregulation of ZPA

A

Results of loss of posterior elements (e.g. little finger/toe)

Upregulation results in additional posterior elements (e.g. polydactyly on hypothenar side)

29
Q

Results of duplication of ZPA

A

Duplication of Posterior elements/disrupted pattern

30
Q

Effect of ZPA on AER maintenance

A

Disruption of ZPA often results in limb growth dysregulation due to its effects on AER

  • ZPA Upregulation causes a limb to be too long
  • ZPA Down-regulation causes a limb to be too short
31
Q

Order of finger formation - Result of disruption of AP Patterning

A

Posterior elements (Little finger/Ulna) are formed before anterior elements (due to spread of ZPA)

Disruption of AP patterning and growth can also lead to loss of anterior elements (e.g. loss of thumb and/or radius)

32
Q

FGF

A

Signal arising from AER causing condensation of cartilage and limb lengthening

33
Q

Sonic Hedgehog

A

Signal Released by ZPA determining AP ais

34
Q

WNT & Engrailed

A

Signals working to define Dorsoventral axis of limbs

35
Q

Why are limb defects usually so complex

A

The different Mediators of limb growth act on each other causing complex deformities involving multiple axes

36
Q

What process occurs to separate the digits in the hand/foot

A

Apoptosis to remove the tissue between cartilagenous blocks

37
Q

Which signalling proteins/areas are involved in digit apoptosis

A

It is dependent on BMP with influence from Sonic Hedgehog and ZPA

38
Q

What is the consequence of a disruption in digit apoptosis and what is its most common presentation

A

Syndactyly (Fingers remain attached to each other), most commonly digits 3, 4 & 5

39
Q

Development of limb bones

A

This occurs through endochondral ossification as mesenchyme begins to form chondrocytes which then lay down a ‘model’ of the bone in cartilage

Like most long bones, the shaft (Diaphysis) forms quite quickly (and is hollow) while the ends (Epiphysis) remain cartilagenous with an epiphyseal growth plate

A blood vessel supplies diaphysis first then later goes into the epiphysis forming a secondary ossification centre

***Phalanges only have one ossification centre

40
Q

What signalling causes endochondral ossification and what external factor disrupts this process

A

FGF Signalling causing chondrocyte proliferation & growth plate maintenance

Steroid hormones switch this off

41
Q

Types of Paraxial Mesoderm and what they develop into

A
  • Sclerotome which develops into vertberal and rib bones
  • Myotome which develops into muscle
  • Dermatome which develops into dermal connective tissue

**C5-T1 Myotomes provide muscles for upper limb

42
Q

Divisions of Myotome

A

Primaxial Myotome

Abaxial Myotome

43
Q

Primaxial Myotome

A

Adjacent to neural tube - affected by signalling factors of neural tube to generate muscle precursors with limited migratory potential

**Muscles nearer to spine

44
Q

Abaxial Myotome

A

Ventrolateral Myoblasts - Responds to signals from adjacent lateral plate mesoderm & ectoderm to give rise to a migratory population

**Gives rise to limb muscles among others

45
Q

Divisions of Primaxial Myotome

A

Epaxial Muscles (Epimere) of the back (Innervated by dorsal rami)

Hypaxial Muscles (Hypomere) of the body wall [prevertebrals, intercostals, "strap muscles", scalenes, geniohyoid, proximal limb girdle (rhomboids, levator scapulae,, latissimus dorsi)]
(Innervated by ventral rami)
46
Q

Myotomes that form the upper and lower limb

A

Upper: C5-T1
Lower: L2-S2

47
Q

Discuss the rotation of the limbs

A

The limb buds lengthen and take their nerve supply with them

The distal limbs then start to flatten into a paddle with the great toe & thumb most anterior

By Week 7 limbs undergo torsion in opposite directions so the elbow is caudal and knee is cranial

As we continue, the upper limb simply lengthens while the lower limb undergoes torsion so that the foot faces downwards - the great toe which was initially anterior is now medial

48
Q

Discuss/Be aware of the dermatome orientation in the upper limb

A
49
Q

Why is the pattern of lower limb dermatomes distorted

A

The torsion that occurs in the lower limb

50
Q

Achondroplastic Dwarfism

A

Bone growth disorder - disproportionate dwarfism with short statute, normal sized torso and short limbs

Occurs in defects in chondrocyte proliferation causing premature closure of epiphyseal growth plates - probably FGF Signalling

Usually a new mutation but can be passed down heterozygously (Dominant)
Homozygotes tend not to survive

51
Q

Spondyloepiphyseal Dysplasia Congenita (SED/SDC)

A

Rare bone growth disorder resulting in dwarfism with characteristic skeletal abnormalities affecting bones of spine and ends of bones

Often also problems with vision/hearing

**Subtype of collagen disease affecting types II & XI (DONT NEED TO KNOW I THINK)

52
Q

Polydactyly

A

Too many fingers - congenital abnormality

53
Q

Syndactyly

A

Webbing of two or more fingers together - congenital abnormality

54
Q

The disruption of what causes most limb growth defects

A

Loss of FGF Signalling

55
Q

Amelia

A

Absence of entire limb

56
Q

Meromelia

A

Absence of part of a limb

57
Q

Phocomelia

A

Short/poorly formed limb

58
Q

Adactyly

A

Absence of digits

59
Q

Ectrodactyly

A

“Lobster-Claw” deformity - variant of adactyly where middle digit is lost

60
Q

What causes polydactyly

A

Usually upregulation of Sonic Hedgehog pathway

61
Q

What causes syndactyly

A

BMP or Sonic Hedgehog disruption

Medicine 2 Week 6 - 11 (54 decks)

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