Limb Development (use notes) Flashcards

1
Q

What are four stages of of pattern formation of cells?

A
  1. morphogenic field is made up 2. Signals to “organizers” are established within positional information 3. recorded position based on cell 4. cells differentiate based on signals
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2
Q

When forelimbs bud and develop they rotate… where as when hind limbs rotate…

A

Forelimb rotate pollex lateral and hind limbs rotate hallux medial

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3
Q

Arm (humerus) or thigh (femur)

A

stylopod

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4
Q

forearm (radius/ulna) or leg (tibia/fibula)

A

Zeugopod

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5
Q

hand or foot

A

autopod

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6
Q

What causes limb field formation in the first month of pregnancy?

A

LPM expresses Fgf10 which causes mitosis and bulging under the ectoderm. This LPM will for the CT, and somites will recruit from hypaxial myotome to become muscle

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7
Q

How do limbs know where to form?

A

Hox genes direct limb formation. Humans (tetrapods) have 4 limbs, so 4 hox clusters from HoxA-HoxD.

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8
Q

What are functions of Hox 4, Hox 5, and HoxC9?

A

Hox 4 and Hox 5 are expressed in forelimbs which induces Tbx5 expression. HoxC9 is expressed in hind limbs causing expression of Pitx1/Tbx4.

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9
Q

Tbx5

A

defines the forelimb field

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10
Q

Defines the hind limb field

A

Tbx4

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11
Q

Hox genes, RA, and Beta catenin all induce Tbx4 and Tbx5 which induce

A

Fgf10 in both fore and hind limbs.

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12
Q

What does Fgf8 do?

A

creates positive feedback loop to Fgf10 to cause more outgrowth

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13
Q

Pitx1 + Tbx4

A

Hind limb growth

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14
Q

Pitx1

A

Hind limb phenotype

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15
Q

In the first month, what is the failed development of one or more limbs?

A

Amelia, which is caused by defect in Wnt3 and blocks beta catenin induction of Tbx4 and Tbx5

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16
Q

In the second month what allows for outgrowth?

A

FGF8 expression leads to formation of apical ectodermal ridge which is at the dorsal/ventral boundary.

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17
Q

What is congenital duplication of the foot and sometimes leg?

A

Diplopodia which is caused by duplicated AER

18
Q

Region of mitotic mesodermal cells beneath AER?

A

Progress Zone which is where limb outgrowth continues right before the begin to differentiate to forelimbs

19
Q

True/False: earlier cells produce distal structures and later cells produce proximal structures

A

FALSE: earlier cells produce proximal, later produce distal

20
Q

True/False: In the two signal model, signals from body wall assign proximal fate and signal from AER assigns distal fate

A

TRUE

21
Q

True/False: Close exposure to FGFs and AER allows cells to differentiate, and removal from progress zone allows cells to undifferentiate in response to proximal and distal signals

A

False: the closer to FGFs and AER the more undifferentiated and removing the progress zone allows cells to differentiate to proximal and distal signals.

22
Q

What creates the AP axis?

A

The zone of polarizing activity or ZPA. It creates the posterior region of limbs

23
Q

… is expressed in the ZPA

A

Sonic Hedgehog which is used to create digits. Digits 5 are made of Shh expressing ZPA cells, digits 3/4 are made of that don’t express ZPA anymore, Digit 2 is made of cells exposed to Shh, and digit 1 is no Shh

24
Q

What is the presence of supernumerary digits?

A

Polydactyly which is point mutation in ZPA regulatory sequence

25
Q

How does ZPA and AER interact?

A

Originally AER and LPM are used to cause early outgrowth. Then ZPA and AER maintain distal outgrowth by expressing FGF4 and Shh (feedback loop)

26
Q

What is an autosomal recessive disorder with congenital amputation of the distal limbs and aplasia of the hands and feet?

A

Acheiropodia which is caused by deletion of ZRS leading to lack of ZPA/AER maintenance

27
Q

Which genes determine dorsal patterning vs ventral patterning?

A

Dorsal is Wnt7a, Lmx-1,and rFng and ventral is BMP and En1. Between expression of these genes is where the AER is

28
Q

… are expressed in apoptotic zones

A

BMPs

29
Q

…are expressed in AER to promote cell survival and antagonize BMP

A

FGFs

30
Q

What is the condition where two or more digits are fused?

A

syndactyly

31
Q

Hoxa and Hoxd regulate … growth. Ex. Investigated in Club foot

A

skeletal growth

32
Q

How does skeleton form?

A

Mesenchyme condenses in limb and increased expression of gap junctions. This formed an early chondrocyte which then goes through endochondral ossification. Secondary ossification replaces cartilage in the epiphysis (growth plate)

33
Q

What is type 2 vs type X collagen?

A

Type 2 is Hyaline which is cartilage and type X is calcified. During the ossification of type 2 it becomes X than type one when perichondrium becomes periosteum

34
Q

What cells make up growth plate?

A

resting which are cartilage progenitors (type 2), proliferating, hypertrophic which are the collagen type X, apoptotic layer, and ossification into type 1

35
Q

Region of cell density induced by Wnt14 and Gdf5 cell death?

A

Joint, and Gdf5 forms the cavity of the joint

36
Q

What is shortening if the hands and feet due to shortened bones?

A

Brachydactyly caused by altered Gdf5 signaling through Bmpr1B

37
Q

How does musculature form?

A

Myoblasts migrate from dermamyotome because of HGF/Scatter expression

38
Q

What forms musculotendinous junctions?

A

derived from LPM, induced by FGF, organized by TGFB, and consolidated by Scleraxis

39
Q

What forms vasculature?

A

from mesoderm aorta or angiogenesis and spreads from meshwork under AER

40
Q

What forms neural invasion?

A

axons guided by pattern signals. In forelimb, cranial nerves target lateral dermatome, in hind limb cranial nerves target medial dermatome.