Limb Development Flashcards
1
Q
When does the upper limb form?
A
Day 24
2
Q
When does the lower limb form?
A
Day 25-26
3
Q
Mesenchymal cells grow out from what section of mesoderm?
A
Lateral Plate Mesoderm
4
Q
Limb buds form deep to a thick band of ectoderm called the:
A
Apical Ectodermal Ridge (AER)
5
Q
Regions of the limb bud consists of:
A
- Stylopod: humerus, femur
- Zeugopod: radius & ulna, tibia & fibula
- Autopod: carpals, metacarpals, phalanges; tarsals, metatarsals, phalanges
6
Q
What are the 3 axes of the limb bud?
A
- Proximal - Distal (shoulder -> digits)
- Cranial - Caudal (Hallux -> Phalanx V)
- Dorsal - Ventral (Dorsum -> Palm)
7
Q
Apical Ectodermal Ridge
A
- Specialized, multilayered epithelial structure located along the ridge of each limb
8
Q
What induces the AER?
A
FGF10 (produced by the mesodermal band)
9
Q
Limb consists of:
A
- Mesoderm/mesenchyme core
- AER at top of limb bud
10
Q
What does AER secrete?
A
FGF8
11
Q
___ feedback loop between FGF8 and FGF10
A
Positive
12
Q
What type of signaling is essential for the initiation of limb development and regulates the outgrowth of the proximodistal axis?
A
FGF
13
Q
Complete/early removal of AER (or FGF8) results in:
A
Arrested limb development (if removed early enough then limb will be completely absent)
14
Q
Removal of AER (of FGF8) at later stages results in:
A
Loss of more distal elemtents
15
Q
Transplanting an AER (or adding FGF8) can result in:
A
Supernumerary limbs (new limb bud/extra limbs)
16
Q
List the 8 Limb Anomalies
A
- Meromelia
- Amelia
- Phocomelia
- Adactyly
- Ectrodactyly
- Polydactyly
- Brachydactyly
- Syndactyly
17
Q
Meromelia
A
- Absence of part of a limb
- Intermediate to late loss of FGF (protein) signaling
18
Q
Amelia
A
- Absence of entire limb
- Early loss of FGF signaling
19
Q
Phocomelia
A
- Loss of long bones with hands and/or feet attached close to the body
- Partial loss of FGF signaling or Hox disruption due to thalidomide exposure during prenatal development
20
Q
Adactyly
A
- Absence of digits
- Late loss of FGF signaling
21
Q
Ectrodactyly
A
- Split hand or split foot anomaly
- “Lobster claw” deformity
- Partial absence of FGF8 from AER
22
Q
Cranial-caudal axis is patterned by the:
A
Zone of Polarizing Activity
23
Q
SHH patterning across digits
A
- Digit 1: SHH independent
- Digit 2: Paracrine SHH signaling (concentration and diffusion)
- Digit 3: Autocrine/paracrine SHH signaling (time of expression and concentration)
- Digits 4 & 5: Autocrine SHH signaling (time of expression)
24
Q
Where is the ZPA located?
A
At the caudal base of the limb bud near future digit 5
25
What regulates the cranial-caudal axis?
SHH signaling from ZPA
26
What signaling molecule is expressed in the ZPA and is sufficient to provide ZPA function?
SHH
27
What happens if ZPA is grafted to cranial limb bud mesoderm (implant SHH producing fibroblasts into the anterior portion of the limb bud)?
Duplicated (mirrored) digits emerge
28
What happens if there is an over-expression of SHH in limb development?
Polydactyly because it establishes a second Zone of polarizing activity and thus more digits than normal
29
What gene regulates the cranial-caudal and proximodistal axes?
Hox genes
30
What Hox genes are expressed within the scapula?
Hox9
31
What Hox genes are expressed within the arm (humerus)?
Hox9 & Hox10
32
What Hox genes are expressed within the ulna, radius, and proximal carpals?
Hox9, Hox10, & Hox 11
33
What Hox genes are expressed within the distal carpals?
Hox9, Hox10, Hox11 & Hox12
34
What Hox genes are expressed within the metacarpals and phalanges?
Hox9, Hox10, Hox11, Hox12 & Hox13
35
Hox9-10 paralogs specify:
Stylopod
36
Hox11 paralogs specify:
Zeugopod
37
Hox12-13 paralogs specify:
Autopod
38
Brachydactyly
- Shortening of the fingers and toes due to unusually short bones
- Genetic changes in the HOXD13 gene or PTHLH gene (parathyroid like hormone)
- Autosomal dominant inheritance
39
What signaling molecule is expressed in the dorsal ectoderm and is a primary regulatory of dorsal fates?
Wnt7a
40
Overexpression of Wnt7a results in:
Dorsalized structures
41
Wnt7a KO mice have ___ paws
Ventralized paws (foot pads form on dorsal surface)
42
What signaling molecule is expressed in the ventral ectoderm?
En1
43
What are the functions of En1?
- Prevents expression of Wnt7a in the ventral part of the limb
- Restricts positioning of the AER to establish the dorsal-ventral axis
44
Removal of interdigital mesenchyme involves?
- Apoptosis of interdigital mesenchyme which frees the digits and allows mobility
- Requires BMP signaling
45
If high levels of BMP signaling:
Increased cell death
46
If low levels of BMP signaling:
Decreased cell death (webbing of digits)
47
When do digital rays form in the hand plates? Foot plates?
- By the 6th week
- By the 7th week
48
What week of development do separate digits form?
8th week
49
Syndactyly
- Fusion of digits because digital rays rail to develop
- two types:
(1) Cutaneous Syndactyly: webbing between digits due to failure to degenerate cutaneous elements; disruption in BMP signaling, lack of apoptosis
(2) Osseous Syndactyly: fusion of bones (synostosis) due to failure of notches to develop between digital rays; autosomal dominant; HoxD13 mutation
50
Dorsal muscle mass forms:
- Extensors and supinators of upper limb
- Extensos and abductors of lower limb
51
Ventral muscle mass forms:
- Flexors and pronators of upper limb
- Flexors and adductors of lower limb
52
What arises from the somatic layer of lateral plate mesoderm?
Limb tendons
53
When does limb innervation begin?
5th week
54
What two branches does a spinal nerve branch into after exiting the spinal cord?
(1) Dorsal ramus -> Epimere
(2) Ventral ramus -. Hypomere & limbs
55
Do motor or sensory neurons innervate first?
Motor neurons
56
Muscles originating in the dorsal muscle mass are innervated by dorsal branches of the:
Ventral Rami
57
Muscles originating in the ventral muscle mass are innervated by ventral branches of the:
Ventral Rami
