Limb Development

Question 1

What is the important time frame for limb bud development?

Answer 1

Day 31-54

Question 2

What gives rise to the CT, blood vessels and main structures of the limb bud?

Answer 2

lateral plate mesoderm

Question 3

What genes help determine between forelimb and hindlimb?

Answer 3

TBX5 (upper limb) and TBX4 (lower limb)

Question 4

What gene mutation causes tetra amelia syndrome?

Answer 4

WNT

Question 5

Which axis does AER (apical ectodermal ridge) influence?

Answer 5

the proximal-distal axis

Question 6

What factor influences the development of the AER?

Answer 6

FGF-10 from the underlying mesoderm which influences the ectoderm to develop into the AER. If no FGF, then the AER will not develop at all and not limb features will form. If AER is already established, then FGF4-8 maintain the progress zone of the mesoderm.

Question 7

Describe the role of AER in proximal-distal limb development?

Answer 7

the AER induces the underlying mesoderm to develop into the limb bud. The region directly below the AER is called the progress zone and the cells in this region are proliferating and not differentiating, but once the AER is no longer over that region, the cells begin to differentiate.

Question 8

What genes are involved in the dorsal-ventral axis?

Answer 8

1. radical fringe-dorsal ectoderm
2. engrailed-1- ventral ectoderm, represses radical fringe
3. SER-2-expressed in border area between the 2

Question 9

What does engrailed 1 do?

Answer 9

represses WNT7a in the ventral ectoderm, thus suppressing the development of dorsal limbs and instead making ventral limbs

Question 10

What is the role of Wnt7a?

Answer 10

it induces expression of LMX1 and leads to dorsal limb development.

Question 11

What is the ZPA?

Answer 11

zone of polarizing activity found in the posterior limb bud mesoderm and determines the development of anterior-posterior limb bud development by influencing the overlying AER. Makes the fingers.

Question 12

What does ZPA make and what are the consequences?

Answer 12

ZPA makes retinoic acid which stimulates production of SHH. SHH upregulates gremlin1 which inhibits BMP allowing production of FGF which maintains SHH in ZPA.

Question 13

What genes play an important role is digit development?

Answer 13

HOX and Gli13 play a huge role in digit development. As dosage of Hox is decreased, more digits are formed. Gli13 decreased then the distal borders of the fingers become more difficult to differentiate and get webbing?

Question 14

How do we get the spaces in between our fingers?

Answer 14

via apopotosis in the AER. Between each of the 5 ectodermal ridges there is a interdigital necrotic zone where AER stops influencing mesoderm, FGF8 down regulated, and retinoic acid someone influences cell death via BMPs.

Question 15

What gives rise to chondrocytes?

Answer 15

mesenchymal cells under influence of SOX9

Question 16

Which somites give rise to the upper limb verse the lower limb?

Answer 16

upper: lower 5 cervical and upper 2 thoracic
lower: lower 4 lumbar and upper 2 sacral

Question 16

What is the role WNT in muscle formation?

Answer 16

• WNT from dorsal spinal cord induces Myf5 in myotome to aid formation of epaxial muscles.
• WNT from body wall ectoderm induces lateral myotome to express MyoD for formation of anterior and limb musculature

Question 16

What gives rise to the musculature of the limb bud?

Answer 16

cells from paraxial mesoderm give rise to somites which consist of dermatome, scleratome and myotome.

Question 16

Do the muscle cells move actively or passively to the limb bud?

Answer 16

ACTIVELY

Question 16

What genes are involved in limb musculature determination?

Answer 16

MyoD and Myf5

Question 16

What is the role WNT in muscle formation?

Answer 16

• WNT from dorsal spinal cord induces Myf5 in myotome to aid formation of epaxial muscles.
• WNT from body wall ectoderm induces lateral myotome to express MyoD for formation of anterior and limb musculature

Question 17

Where do the nerve cells that innervate the skeletal muscle cells arise from?

Answer 17

neuroepithelial cells of the neural tube (mantle layer of basal plate). Neurons are called alpha motor neuros or ventral horn cells

Question 17

What do the ventral rami cells form?

Answer 17

• upper limb ventral rami form the brachial plexus

- lower limb ventral rami form the lumbosacral plexus

Question 18

What happens when there is loss of ectopic SHH?

Answer 18

mirrorimage duplication in fingers

Question 19

What happens if there is total loss of FGF vs 1 copy loss?

Answer 19

total loss=no limb

copy loss= truncated limb

Question 20

What happens if there is loss of WNT7a?

Answer 20

won’t have dorsal structures

Question 21

What happens is there is no engrailed1?

Answer 21

WNT7 is not repressed therefore we get dorsal structures forming where there should be ventral structures

Question 22

What is thalidomide?

Answer 22

Drug that was used for morning sickness and instead created severe birth defects because it inhibited FGF and VEGF. Was a glutamic acid derivative.