Exam 4 - Limb Development Flashcards

1
Q

Limb development is a good example of what process in embryonic development?

A

Pattern Formation

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2
Q

Pattern formation

A

Distinct body parts are arranged in a very predictable pattern , arising from the same embryonic structures.

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3
Q

What 6 things contribute to general pattern formation?

A
  1. cell division at unequal rates
  2. cell aggregation
  3. cell growth - elongation
  4. programmed cell death
  5. induction by chemical gradients
  6. homotic genes = pattern forming genes
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4
Q

What do homeotic (Hox) genes do?

A

They create regional differences in anterioposterior body pattern during embryonic development.

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5
Q

What could happen if one or more hox genes were mutated?

A

Certain body parts could end up getting replaced by part found elsewhere normally

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6
Q

How many base pairs does a homeotic gene contain?

A

1000 approx

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7
Q

where does the term hox gene come from?

A

from the 180 bp consensus sequences on homeotic genes called the homebox

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8
Q

What do the 180 bp consensus seq code for?

A

60 amino acid domains called homeodains

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9
Q

What do homeodomains do?

A

They bind to DNA (this means that the product of homeotic genes are transcription factors

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10
Q

What are the three axes in limb development?

A
  1. proximal-distal
  2. dorsal-ventral
  3. anterior-posterior
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11
Q

What is a limb field?

A

It s the limb fate map = limb forming + limb inducing cells. They are concentric circles

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12
Q

What does it mean to say that limb fields are a type of regulative development?

A

It means that the cell fate of the cells within it are flexible, and that it will compensate if cells are lost or gained at any point

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13
Q

At what point in human development would you expect a limb bud to appear?

A

At approximately the 5th week

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14
Q

Cells migrate from where to initiate limb formation?

A

mesenchyme cells from the hypaxial myotome (part of the somite) as well as cells from the somatic plate mesoderm

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15
Q

What part of the limb do the mesencyme cells from the hypaxial myotome eventually aggregate to form?

A

The muscles of the limb

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16
Q

What part of the limb do the somatic plate mesoderm cells eventually become?

A

Cartilage and then eventually bone in the limbs

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17
Q

Between what two things is there reciprocal interaction in limb formation?

A

Between the lateral plate mesoderm and the mesenchyme cells

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18
Q

What do the mesenchyme cells in limb development secrete in order to induce initial, generic limb formation?

A

FGF-10

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19
Q

What do the somatic plate mesoderm cells express in order to induce limb formation?

A

They express various combination of hox genes

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20
Q

What is the hox gene and chemical gradient concentration needed to create an arm?

A

Hox d9 > hox b9 > hox c9 as well as high concentrations of noggin/Otx2

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21
Q

What is the hox gene and chemical gradient conc. needed to create a leg?

A

Hox d9 = c9 > b9 as well as high concentrations of BFGF

22
Q

What is needed in order to not create an arm or a leg, but rather be left with a flank?

A

hox b9 = hox c9 as well as equal concentrations of noggin/otx2 and BFGF

23
Q

What were to occur in limb development if the limb field were somehow split?

A

Limb twins would arise

24
Q

What does AER stand for?

A

apical ectodermal ridge

25
What induces the formation of the AER?
the limb bud mesenchyme from myotome and somatic plate
26
What is the apical ectodermal ridge?
It is a ridge of elongated cells along the antero-posterior axis
27
How does the AER induce the proliferation of mesenchyme cells withing the "progress zone"?
By secreting FGF-4
28
Continued growth of the AER requires ___________________________
stimulation from the mesenchyme
29
Where are the AER and progress zone located in developing limb?
They are always on the distal end of the developing limb, leaving daughter cells as it elongates
30
What process is essential to proper limb development due to the needs that the cells have for nutrients
Angiogenesis, off of the dorsal aorta
31
Thalidomide "flipper" babies
In the 1960's the drug Thalidomide was perscribed to pregnant women, it was later discovered that the drug has the side affect of blocking angiogenesis. This resulted in babies being born with hands and feet but no limbs.
32
When does the dorsoventral axis pattern occur?
It is initiated before the limb bud even forms
33
Somites dorsalize the ectoderm prior to limb bud formation and force it to express?
Wnt-7
34
What establishes the dorsal-ventral axis?
The concentration gradient of Wnt-7 expressed by dorsal ectoderm
35
What does the expression of radical fringe by the dorsal ectoderm result in?
It results in the formation of knuckles and nails
36
What does the ventral ectoderm express in order to induce the formation of palms and pads?
engrailed-1
37
What does the ectoderm between the ventral ectoderm and the dorsal ectoderm become?
It becomes the apical ectodermal ridge
38
Without _______ both sides of the limb would be ventral
Wnt-7
39
What does ZPA stand for?
Zone of polarizing (posteriorizing) activity
40
Where is the ZPA located?
at the posterior edge of the limb bud, it travels along the limb along with the AER and progress zone
41
What causes the polarizing (posteriorizing) activity that is occurring in limb formation?
The secretion of Shh by the zone of polarizing activity (ZPA)
42
What does the result of the Shh gradient created by the ZPA?
It induces a "nested" set of hox genes to be expressed in the limb bud
43
What hox gene combination results in the formation of the thumb?
Hox d9
44
What hox gene combination results in the formation of the 2nd (index) finger?
Hox d9 and d10
45
What hox gene combination results in the formation of the 3rd (middle) finger?
Hox d9, d10, and d11
46
What hox gene combination results in the formation of the 4th (ring) finger?
Hox d9, d10, d11, and d12
47
What hox gene combination results in the formation of the 5th (pinkie) finger?
Hox d9, d10, d11, d12, d13
48
How do fingers separate?
Apoptosis = programmed cell death
49
What is syndactyly?
The presence of "webbed" hands or feet due to the fact that apoptosis between the digits did not occur during embryonic development
50
All limbs in the embryo begin bending?
outward
51
How do the upper limbs rotate?
They rotate 90 degrees in order to point/bend dorsally
52
How do the lower limbs rotate?
They rotate 90 degrees in order to point/bend ventrally