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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
What parts of the embryo initiates Dorso-Ventral Patterning of the limbs
WNT7 is expressed on the Dorsal Surface ENGRAILED-1 and Bone Morphogenic Protein are expressed on the Ventral surface
26
Relation of Dorso-Ventral Patterning with Proximo-Distal Outgrowth; and relevance
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
What part of the embryo initiates Anterior-Posterior Limb Patterning
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
Results of loss/upregulation of ZPA
Results of loss of posterior elements (e.g. little finger/toe) Upregulation results in additional posterior elements (e.g. polydactyly on hypothenar side)
29
Results of duplication of ZPA
Duplication of Posterior elements/disrupted pattern
30
Effect of ZPA on AER maintenance
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
Order of finger formation - Result of disruption of AP Patterning
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
FGF
Signal arising from AER causing condensation of cartilage and limb lengthening
33
Sonic Hedgehog
Signal Released by ZPA determining AP ais
34
WNT & Engrailed
Signals working to define Dorsoventral axis of limbs
35
Why are limb defects usually so complex
The different Mediators of limb growth act on each other causing complex deformities involving multiple axes
36
What process occurs to separate the digits in the hand/foot
Apoptosis to remove the tissue between cartilagenous blocks
37
Which signalling proteins/areas are involved in digit apoptosis
It is dependent on BMP with influence from Sonic Hedgehog and ZPA
38
What is the consequence of a disruption in digit apoptosis and what is its most common presentation
Syndactyly (Fingers remain attached to each other), most commonly digits 3, 4 & 5
39
Development of limb bones
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
What signalling causes endochondral ossification and what external factor disrupts this process
FGF Signalling causing chondrocyte proliferation & growth plate maintenance Steroid hormones switch this off
41
Types of Paraxial Mesoderm and what they develop into
- 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
Divisions of Myotome
Primaxial Myotome | Abaxial Myotome
43
Primaxial Myotome
Adjacent to neural tube - affected by signalling factors of neural tube to generate muscle precursors with limited migratory potential **Muscles nearer to spine
44
Abaxial Myotome
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
Divisions of Primaxial Myotome
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
Myotomes that form the upper and lower limb
Upper: C5-T1 Lower: L2-S2
47
Discuss the rotation of the limbs
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
Discuss/Be aware of the dermatome orientation in the upper limb
49
Why is the pattern of lower limb dermatomes distorted
The torsion that occurs in the lower limb
50
Achondroplastic Dwarfism
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
Spondyloepiphyseal Dysplasia Congenita (SED/SDC)
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
Polydactyly
Too many fingers - congenital abnormality
53
Syndactyly
Webbing of two or more fingers together - congenital abnormality
54
The disruption of what causes most limb growth defects
Loss of FGF Signalling
55
Amelia
Absence of entire limb
56
Meromelia
Absence of part of a limb
57
Phocomelia
Short/poorly formed limb
58
Adactyly
Absence of digits
59
Ectrodactyly
"Lobster-Claw" deformity - variant of adactyly where middle digit is lost
60
What causes polydactyly
Usually upregulation of Sonic Hedgehog pathway
61
What causes syndactyly
BMP or Sonic Hedgehog disruption

Medicine 2 Week 6 - 11 (54 decks)

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