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ANAT 381 Experimental Embryology > Limb Development and Disrupting Embryonic Development > Flashcards

Limb Development and Disrupting Embryonic Development Flashcards

1
Q

Each of the following limb development regions is responsible for which part?
a. Stylopod
b. Zeugopod
c. Autopod

A

a. Humerus
b. Ulna and radius
c. Carpals and digits

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2
Q

What are the critical regions in the developing limb bud?

A

Progress zone, zone of polarizing activity (ZPA), apical ectodermal ridge (AER)

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3
Q

Where is the ZPA located?

A

Posterior mesenchyme of the limb bud

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4
Q

Where is the AER located?

A

At the boundary of dorsal and ventral sides of the limb bud

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5
Q

AER is required for patterning which axes of the limb bud?

A

Proximal-distal, dorsal-ventral, anterior-posterior

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6
Q

What can replace the AER activity?

A

Implantation of FGF bead

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7
Q

RA concentration is higher on the __________ axis and Fgf/Wnt concentration is higher on the ___________ axis

A

Proximal; distal

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8
Q

Which genes are linked to the stylopod, zeugopod and autopod?

A

Meis for stylopod, Hox11 for zeugopod and Hox13 for autopod

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9
Q

What is RA responsible for in limb bud PD patterning?

A

RA activates Meis genes and promotes proximal formation of the limb bud

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10
Q

What is FGF/Wnt responsible for in limb bud PD patterning?

A

FGF initiates Hox13 genes and promotes distal formation of the limb bud

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11
Q

Hoxa11/Hoxd11-deficient mice are missing which limb part?

A

Zeugopod

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12
Q

In humans, homozygous mutation in Hoxd13 causes which disorder?

A

Polysyndactyly (fused digits)

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13
Q

What does AER activity require?

A

Limb bud mesenchyme

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14
Q

PD specification of the limb is correlated with what factor?

A

The age of the progress zone mesenchyme

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15
Q

___________ and ___________ is expressed in dorsal ectoderm, ___________ is expressed in ventral ectoderm

A

Wnt7a; Lmx1; En-1

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16
Q

A loss of Lmx1 causes what effect?

A

Ventralized dorsal side, causing two ventral sides

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17
Q

Knockout of Engrailed causes what effect on the limb?

A

Loss of ventral patterning

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18
Q

Addition of AER tissue to the forelimb mesenchyme causes what effect?

A

Digit duplication

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19
Q

ZPA transplantation of mouse ZPA to chick causes what effect?

A

Formation of digits

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20
Q

What is expressed in ZPA?`

A

Shh

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21
Q

Transplanting ZPA of Shh beads causes what effect?

A

Mirror image duplication

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22
Q

Identify the response to Shh signaling to the digits
a. Shh independent
b. Differentiation dependent on Shh concentration (paracrine)
c. Shh-dependent; time-dependent (autocrine)

A

a. Digit 1
b. Digits 2 and 3
c. Digits 4 and 5

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23
Q

(Fgf8/Shh) is expressed in the ZPA after (Fgf8/Shh) is expressed in the AER

A

Shh; Fgf8

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24
Q

What is the mechanism of FGF activating Shh with the activity of Grem1?

A

Grem1 stimulates FGF when FGF is low
High FGF stimulates Shh expression and represses Grem1 activity
Low Grem1 activity decreases FGF expression

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25
Q

What determines limb identity?

A

Limb mesenchyme

26
Q

Tbx5 is expressed in which limb?

27
Q

Tbx6 is expressed in which limb?

28
Q

Early knockout of Tbx5 causes what effect?

A

Forelimbs do not develop

29
Q

Later knockout of Tbx5 after E9.5 causes what effect?

A

Forelimbs develop normally

30
Q

What happens if Tbx5 is knocked out and replaced with Tbx4 or Pitx1?

A

Ectopic Tbx4 in forelimb bud led to normal development of forelimb
Ectopic Pitx1 in forelimb bud led to no forelimb development

31
Q

Tbx4/5 are required for forelimb/hindlimb bud _________, but not identity

A

Initiation

32
Q

Pitx1 is important for the _____________ bud development

33
Q

Every _______ minutes, there is a baby born in the US with a birth defect

34
Q

What is the percentage of human cleavage-stage embryos implanting?

35
Q

What is the percentage of the survival of embryos that implant?

36
Q

What is the percentage of live births that have a recognizable birth defect?

37
Q

Congenital anomalies account for what percentage of annual neonatal deaths?

38
Q

Identify the description to either embryo or fetus
a. First 8 weeks in humans
b. Weeks 9-40 in humans
c. Period of development during which the organism does not resemble the adult
d. Growth and refinement

A

a. Embryo
b. Fetus
c. Embryo
d. Fetus

39
Q

When is the risk of defects highest?

A

Organogenesis

40
Q

What are the periods of sensitivity for abnormal development in the CNS, upper and lower limbs?

A

CNS: Weeks 3 to full term
Upper and lower limbs: Weeks 4 1/2 to 9

41
Q

What is genetic heterogeneity?

A

Similar phenotypes caused by different genes

42
Q

What is phenotypic heterogeneity?

A

Same mutation causes different phenotypes in different individuals

43
Q

What are some causes of congenital anomalies/birth defects?

A

Genetic factors, environmental factors, stochastic factors

44
Q

Dysplasia is an abnormal organization of cells into ___________ and its morphological result

45
Q

Deformations are caused by what factors?

A

Mechanical forces or physical environment

46
Q

Malformations are caused by what factor?

A

Intrinsically abnormal development process

47
Q

Disruptions are caused by what factor?

A

Interference of an originally normal process

48
Q

Clubfoot is potentially caused by _____________

A

Oligohydraminos

49
Q

What is the name of the limb malformation caused by a mutation in Tbx5 and characterized by upper limb anomalies?

A

Holt-Oram Syndrome

50
Q

Which drug was used to treat influenza, as a sedative and to treat nausea and vomiting during pregnancy?

A

Thalidomide

51
Q

What limb disruption is caused by the use of Thalidomide?

A

Upper limb anomalies

52
Q

Limb disruptions occur _________ during limb development and limb deformations occur ____________ during limb development

A

Early; later

53
Q

What is an agent that affects morphogenesis, development and differentiation through cell death, failed cell interactions or alterations of cell movements?

54
Q

What are 3 considerations of teratogens?

A

Critical periods of development, dosage of the drug and genotype of the embryo

55
Q

What are other teratogens that exist?

A

Isotretinoin, alcohol, endocrine disruptors, Rubella virus

56
Q

How are the effects of thalidomide tested?

A

Testing of drugs in pregnant experimental animals

57
Q

What is the syndrome caused by fetal exposure to alcohol?

A

Fetal alcohol syndrome

58
Q

What are the symptoms of fetal alcohol syndrome?

A

Poor growth, decreased muscle tone and poor contraction, delayed development and problems in thinking, speech, movement or social skills

59
Q

What are the phenotypes of ethanol-induced dysmorphology?

A

FAS, HPE, HPE plus cleft lip

60
Q

Retinoic acid induces _________________

A

Holoprosencephaly (HPE)

61
Q

Hydrocephaly, microcephaly and increased risk of spontaneous abortions are congenital anomalies caused by ______________

A

Isotretinoin

62
Q

What were the goals of the iPLEDGE program?

A

Ensure that no pregnant woman starts taking Isotretinoin and no woman taking Isotretinoin becomes pregnant

ANAT 381 Experimental Embryology (24 decks)

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