Limb Development

Question 1

When does the upper limb form?

Answer 1

Day 24

Question 2

When does the lower limb form?

Answer 2

Day 25-26

Question 3

Mesenchymal cells grow out from what section of mesoderm?

Answer 3

Lateral Plate Mesoderm

Question 4

Limb buds form deep to a thick band of ectoderm called the:

Answer 4

Apical Ectodermal Ridge (AER)

Question 5

Regions of the limb bud consists of:

Answer 5

• Stylopod: humerus, femur
• Zeugopod: radius & ulna, tibia & fibula
• Autopod: carpals, metacarpals, phalanges; tarsals, metatarsals, phalanges

Question 6

What are the 3 axes of the limb bud?

Answer 6

• Proximal - Distal (shoulder -> digits)
• Cranial - Caudal (Hallux -> Phalanx V)
• Dorsal - Ventral (Dorsum -> Palm)

Question 7

Apical Ectodermal Ridge

Answer 7

• Specialized, multilayered epithelial structure located along the ridge of each limb

Question 8

What induces the AER?

Answer 8

FGF10 (produced by the mesodermal band)

Question 9

Limb consists of:

Answer 9

• Mesoderm/mesenchyme core
• AER at top of limb bud

Question 10

What does AER secrete?

Answer 10

FGF8

Question 11

___ feedback loop between FGF8 and FGF10

Answer 11

Positive

Question 12

What type of signaling is essential for the initiation of limb development and regulates the outgrowth of the proximodistal axis?

Answer 12

FGF

Question 13

Complete/early removal of AER (or FGF8) results in:

Answer 13

Arrested limb development (if removed early enough then limb will be completely absent)

Question 14

Removal of AER (of FGF8) at later stages results in:

Answer 14

Loss of more distal elemtents

Question 15

Transplanting an AER (or adding FGF8) can result in:

Answer 15

Supernumerary limbs (new limb bud/extra limbs)

Question 16

List the 8 Limb Anomalies

Answer 16

• Meromelia
• Amelia
• Phocomelia
• Adactyly
• Ectrodactyly
• Polydactyly
• Brachydactyly
• Syndactyly

Question 17

Meromelia

Answer 17

• Absence of part of a limb
• Intermediate to late loss of FGF (protein) signaling

Question 18

Amelia

Answer 18

• Absence of entire limb
• Early loss of FGF signaling

Question 19

Phocomelia

Answer 19

• 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

Question 20

Adactyly

Answer 20

• Absence of digits
• Late loss of FGF signaling

Question 21

Ectrodactyly

Answer 21

• Split hand or split foot anomaly
• “Lobster claw” deformity
• Partial absence of FGF8 from AER

Question 22

Cranial-caudal axis is patterned by the:

Answer 22

Zone of Polarizing Activity

Question 23

SHH patterning across digits

Answer 23

• 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)

Question 24

Where is the ZPA located?

Answer 24

At the caudal base of the limb bud near future digit 5

Question 25

What regulates the cranial-caudal axis?

Answer 25

SHH signaling from ZPA

Question 26

What signaling molecule is expressed in the ZPA and is sufficient to provide ZPA function?

Answer 26

SHH

Question 27

What happens if ZPA is grafted to cranial limb bud mesoderm (implant SHH producing fibroblasts into the anterior portion of the limb bud)?

Answer 27

Duplicated (mirrored) digits emerge

Question 28

What happens if there is an over-expression of SHH in limb development?

Answer 28

Polydactyly because it establishes a second Zone of polarizing activity and thus more digits than normal

Question 29

What gene regulates the cranial-caudal and proximodistal axes?

Answer 29

Hox genes

Question 30

What Hox genes are expressed within the scapula?

Answer 30

Hox9

Question 31

What Hox genes are expressed within the arm (humerus)?

Answer 31

Hox9 & Hox10

Question 32

What Hox genes are expressed within the ulna, radius, and proximal carpals?

Answer 32

Hox9, Hox10, & Hox 11

Question 33

What Hox genes are expressed within the distal carpals?

Answer 33

Hox9, Hox10, Hox11 & Hox12

Question 34

What Hox genes are expressed within the metacarpals and phalanges?

Answer 34

Hox9, Hox10, Hox11, Hox12 & Hox13

Question 35

Hox9-10 paralogs specify:

Answer 35

Stylopod

Question 36

Hox11 paralogs specify:

Answer 36

Zeugopod

Question 37

Hox12-13 paralogs specify:

Answer 37

Autopod

Question 38

Brachydactyly

Answer 38

- 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

Question 39

What signaling molecule is expressed in the dorsal ectoderm and is a primary regulatory of dorsal fates?

Answer 39

Wnt7a

Question 40

Overexpression of Wnt7a results in:

Answer 40

Dorsalized structures

Question 41

Wnt7a KO mice have ___ paws

Answer 41

Ventralized paws (foot pads form on dorsal surface)

Question 42

What signaling molecule is expressed in the ventral ectoderm?

Answer 42

En1

Question 43

What are the functions of En1?

Answer 43

- Prevents expression of Wnt7a in the ventral part of the limb - Restricts positioning of the AER to establish the dorsal-ventral axis

Question 44

Removal of interdigital mesenchyme involves?

Answer 44

- Apoptosis of interdigital mesenchyme which frees the digits and allows mobility - Requires BMP signaling

Question 45

If high levels of BMP signaling:

Answer 45

Increased cell death

Question 46

If low levels of BMP signaling:

Answer 46

Decreased cell death (webbing of digits)

Question 47

When do digital rays form in the hand plates? Foot plates?

Answer 47

- By the 6th week - By the 7th week

Question 48

What week of development do separate digits form?

Answer 48

8th week

Question 49

Syndactyly

Answer 49

- 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

Question 50

Dorsal muscle mass forms:

Answer 50

- Extensors and supinators of upper limb - Extensos and abductors of lower limb

Question 51

Ventral muscle mass forms:

Answer 51

- Flexors and pronators of upper limb - Flexors and adductors of lower limb

Question 52

What arises from the somatic layer of lateral plate mesoderm?

Answer 52

Limb tendons

Question 53

When does limb innervation begin?

Answer 53

5th week

Question 54

What two branches does a spinal nerve branch into after exiting the spinal cord?

Answer 54

(1) Dorsal ramus -> Epimere (2) Ventral ramus -. Hypomere & limbs

Question 55

Do motor or sensory neurons innervate first?

Answer 55

Motor neurons

Question 56

Muscles originating in the dorsal muscle mass are innervated by dorsal branches of the:

Answer 56

Ventral Rami

Question 57

Muscles originating in the ventral muscle mass are innervated by ventral branches of the:

Answer 57

Ventral Rami