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템 > Limb Development > Flashcards

Limb Development Flashcards

1
Q

Musculature is derived from what embryonic precursor?

A

Paraxial mesoderm –> somite –> myotome

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2
Q

Bones are derived from what embryonic precursor?

A

Lateral plate mesoderm –> somatic region

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3
Q

Tendons are derived from what embryonic precursor?

A

Lateral plate mesoderm –> somatic region

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4
Q

By what week of development are both limb buds present?

A

Week 4

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5
Q

By what week in development does primary ossification of the limbs begin?

A

Week 12

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6
Q

By what week in development do hand/foot plates appear and chondrification begins?

A

Week 5

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7
Q

By what week in development does the embryo begin showing separation of digits?

A

8th week

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8
Q

By what week in development do digital rays of feet appear, osteogenesis begins, and rotation of limbs occurs?

A

7th week

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9
Q

By what week of development do digital rays of hands appear and limb skeleton is cartilaginous?

A

6th week

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10
Q

Which limbs form first, upper or lower?

A

Upper limb buds form at 24 days

Lower limb buds form at 28 days

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11
Q

Limb bud formation is due to proliferation of __________ cells from ______ ______ mesoderm (somatic region)

This causes the limb bud to bulge outward

A

Mesenchymal; lateral plate

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12
Q

What are the 3 axes of the limb buds?

A

Proximal/distal

Cranial/caudal

Dorsal/ventral

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13
Q

What structures are associated with the proximal/distal axis of the upper limb bud?

A

Shoulder = proximal

Digits = distal

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14
Q

What structures are associated with the cranial/caudal axis of the upper limb bud?

A

Cranial = hallux

Caudal = phalanx 5

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15
Q

What structures are associated with the dorsal/ventral axis of the upper limb bud?

A

Dorsal = dorsum of hand

Ventral = palm of hand

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16
Q

What is the stylopod as it refers to limb structure?

A

Humerus or femur

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17
Q

What is the zeugopod as it relates to limb structure?

A

Radius + ulna; tibia + fibula

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18
Q

What is the autopod as it relates to limb structure?

A

Hand; foot

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19
Q

What molecular interaction is resposible for initiating limb bud outgrowth?

A

Fgf10 from mesenchyme (lateral plate mesoderm) activates Wnt signaling

Wnt then induces Fgfs in the ectoderm - this is a positive feedback loop

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20
Q

What region of the limb bud controls proximal-distal outgrowth of the limb?

A

Apical Ectodermal Ridge (AER)

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21
Q

What does the AER secrete that allows for continued limb outgrowth?

A

Fgf8

[Fgf soaked beads induce supernumerary limbs; Fgfs can mimic the functions of the AER itself]

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22
Q

What would be the result of experimental removal of the AER?

A

Limb development ceases

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23
Q

What would be the result of experimental addition of AER material?

A

Wing/limb is duplicated

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24
Q

What would be the result of experimental replacement of upper limb mesenchyme with lower limb mesenchyme?

A

Leg develops in place of arm

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25
What would be the result of experimental replacement of limb mesenchyme with nonlimb mesenchyme?
AER regresses; limb development ceases
26
What would be the result of AER replacement by FGF bead?
Wing/limb develops normally
27
The AER is responsible for limb outgrowth, but not limb identity. What gene clusters are expressed in limb buds that correspond to identity of structures?
Hox gene clusters
28
Hox11 paralogs are responsible for formation of what aspect of limb structure?
Zeugopod
29
Hox9-10 paralogs are responsible for formation of what aspect of limb structure?
Stylopod
30
Hox12-13 paralogs are responsible for formation of what aspect of limb structure?
Autopod
31
__________ = genes related to each other due to descent from a common ancestral DNA sequence (commonly duplication)
Paralogues
32
Hox expression pattern correlates with the identity of elements along the __________-________ axis
Proximal-distal
33
________-_______ axis specification is the earliest restriction of cell fates in the limb; it occurs before limb bud outgrowth even begins
Anterior-posterior
34
A-P axis specification is the earliest restriction of cell fates in the limb. What is responsible for patterning these cell fates?
Zone of polarizing activity (ZPA)
35
A-P axis specification is the earliest restriction of cell fates in the limb. Cell fates are patterned by the zone of polarizing activity (ZPA). What important signaling factor is expressed in the ZPA?
Sonic hedgehog (Shh)
36
T/F: SHH is expressed in the ZPA and is sufficient on its own to provide ZPA function
True! When the ZPA is grafted to anterior limb bud mesoderm, duplicated digits emerge
37
What signal factor is the primary regulator of the dorsal-ventral axis of the limb bud?
Wnt7a
38
Wnt7a is the primary regulator of the dorsal-ventral limb bud axis. It is responsible for __________ structures. Wnt7a knockouts have ________ paws. It is itself controlled by ________.
Dorsalizing Ventralized Lmx1b
39
Formation of individual digits occurs through what cellular process?
Apoptosis
40
At what day of development does formation of digits via apoptosis begin?
Day 48, mostly complete by day 56
41
Formation of digits occurs through apoptosis beginning at day 48 of development. This requires what signaling factor?
BMP [increased BMP --> increased cell death, areas with decreased BMP have decreased cell death - results in webbed digits]
42
Prior to limb rotation, the limbs are oriented with the ventral surfaces (flexors) facing __________, and the dorsal surfaces (extensors) facing __________
Medially Laterally [both are continueous with the ventral and dorsal surfaces of the embryonic trunk at this point]
43
During which week in development does limb rotation occur?
Week 7
44
Rotation of the limbs occurs as torsion in the ________ and _________ diaphysis
Femoral; humeral
45
Beginning in week 7 of development, the upper limbs undergo ________ rotation, while the lower limbs rotate _________
Lateral; medially
46
Describe the end result of limb rotation in the upper extremity
Upper extremity rotates 90 degrees laterally Flexor compartment faces anteriorly and extensors are posterior
47
Describe the end result of limb rotation in the lower extremity
Lower extremity rotates 90 degrees medially Flexor compartment is posterior and extensors are anterior (this is opposite the upper limb!)
48
What is responsible for the irregular appearance of the dermatomes in the limbs?
Limb rotation
49
Limb musculature is derived from the __________ cells of the somites
Dorsolateral
50
Is limb musculature derived from epimere or hypomere?
Hypomere
51
****What do limb tendons arise from?****
Lateral plate mesoderm
52
The dorsal muscle mass forms what muscles in the upper and lower limbs?
Upper limb: extensors and supinators Lower limb: extensors and abductors
53
The ventral muscle mass forms what muscles in the upper and lower limbs?
Upper limb: flexors and pronators Lower limb: flexors and adductors
54
Bone formation in the limbs is considered endochondral ossification from a ________ cartilage precursor
Hyaline
55
T/F: Limb innervation begins with sensory fiber outgrowth first
False Axons within ventral rami (MOTOR) innervate limb muscles during the 5th week
56
Why is it important that motor axons form first?
The sensory axons follow the motor axons and use them for guidance
57
Once motor and sensory axons have been established during the process of limb innervation, what is the next step?
Neural crest cells form Schwann cells which are responsible for myelination of the newly formed axons
58
A sorting process must occur during the process of limb innervation. Axons cranial to the limb innervate _________ musculature. Axons caudal to the limb innervate __________ musculature.
Dorsal Ventrocaudal
59
What are the 2 sources for blood supply to the limbs?
Axial artery Remodeling of branches of 7th cervical intersegmental a. and 5th lumbar intersegmental a.
60
The 2 sources of blood supply to the limbs are the axial a. and the remodeling of branches of the 7th cervical intersegmental a. and the 5th lumbar intersegmental a. What is the axial a. derived from and describe its length
Axial a. develops de novo within the central axis of the limb (by day 30 in the upper limb and day 36 in the lower limb) It extends the length of the limb
61
The 2 sources of blood supply to the limbs are the axial a. and the remodeling of branches of the 7th cervical intersegmental a. and the 5th lumbar intersegmental a. Where do the remodeling branches originate, branch, and join?
They originate within surrounding mesoderm and join the dorsal aorta They then branch and join an axial a.
62
The primary blood supply to the upper limb comes from the axial artery. What is the corresponding primary blood supply in the lower limb?
Ischiadic a.
63
T/F: Limb anomalies occur in 1:200 live births and typically can be corrected surgically
True
64
__________ = limb anomaly characterized by the absence of part of a limb d/t late or partial loss of FGF signaling
Meromelia
65
___________ = limb anomaly characterized by absence of an entire limb due to early loss of FGF signaling
Amelia
66
__________ = limb anomaly characterized by presence of supernumerary digits, inherited as a dominant trait
Polydactyly
67
Polydactyly occurs due to overexpression of _______, which establishes a second ______
SHH; ZPA
68
Polydactyly most commonly occurs at which of the following areas? ``` A. Medial B. Lateral C. Dorsal D. Ventral E. A and B ```
E. A and B [note that with the foot specifically, the extra toe is usually on the lateral side]
69
Describe characteristics of extra digits formed in polydactyly
Extra digit(s) are usually incompletely formed and lack normal muscular development
70
___________ = limb anomaly characterized by absence of digits
Adactyly
71
__________ = limb anomaly characterized by fusion of digits
Syndactyly
72
Syndactyly is characterized by the fusion of digits. What are the 2 types of syndactyly?
Cutaneous syndactyly | Osseous syndactyly
73
What type of syndactyly is characterized by the fusion of bones (synostosis)?
Osseous syndactyly
74
What type of syndactyly is characterized by simple webbing between digits due to failure of apoptosis to degenerate this webbing?
Cutaneous syndactyly
75
Syndactyly may occur if _______ ______ fail to develop. It is inherited as a simple _______ _______ trait. May occur due to ______ disruption or _______ mutation.
Digital rays Autosomal dominat BMP; HoxD13
76
_________ is a limb anomaly characterized by absence of long bones, with rudimentary hands and feet due to partial loss of FGF signaling or Hox disruption
Phacomelia
77
____________ is a non-genetic cause of limb anomalies as it is a drug that was used as a sedative and anti-nauseant in pregnant women between 1957 and 1962. It is now contraindicated in pregnancy but it continues to be used as a chemotherapy drug for its ability to inhibit angiogenesis.
Thalidomide
78
What limb anomaly is also known as split-hand or split-foot anomaly?
Ectrodactyly (lobster-claw deformity) [may be due to a variety of genetic mutations: DLX5/6, P63, FGF8, etc.]
79
_________ ________ = adhesions between amnion and affected fetal structures that may cause limb anomalies
Amniotic bands
80
What is the medical term for "club foot"?
Talipes equinovarus
81
What condition, characterized by a reduction in amniotic fluid, may reduce fetal movement leading to amniotic bands and/or talipes equinovarus?
Oligohydramnios

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