Genetic and Environmental Influences on Early Human Development Flashcards Preview

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Flashcards in Genetic and Environmental Influences on Early Human Development Deck (90):
1

Fewer than 1/2 fertilized human eggs implant and of that, what fraction will give rise to an infant?

1/3

2

Structural abnormalities that can be caused by genetic factors or by environmental factors, or both

Congenital malformations (present at birth)

3

About 6% of individuals are born with congenital malformations. What percentage of perinatal deaths are caused by such abnormalities?

20%

4

The field that has emerged to study abnormal development in embryos

-investigates the causes of congenital abnormalities/birth defects

Teratology

5

7% of congenital abnormalities are known to be caused by

-can be chemical toxins, infections, or maternal deficiency

Teratogenic agents

6

Will often kill embryo in first two prenatal weeks or lead
to spontaneous abortions in the first 6-8 weeks of gestation

Teratogenic agents

7

Teratogens can cause organ-specific abnormalities from days

15-60

8

Genetic factors cause 20-25% of birth defects, where as environmental factors account for

5-15%

9

Most cases of Down syndrome are caused by a deficit in

-produces gamete with 2 copies of chromosome 21

Meiosis I

10

Another cause of Down Syndrome that occurs when the q arms of chromosomes 14 and 21 fuse

-No symptoms

Robertsonian translocation

11

Has the symptoms of distinct facial features, congenital
heart disease, mental and growth retardation

Down Syndrome

12

Almost all alterations in chromosome number will be lethal in

Early embryo

13

Besides trisomy 21, what are two other trisomies where affected individuals survive post natally?

Trisomy 13 and trisomy 18

14

Can be a major result of abnormal genetic composition (esp. trisomy 13)

Midline defects

15

Cleft lip and palate and CNS malformations are characteristic of

Trisomy 13

16

Tend to survive longer with trisomy 18

Females

17

Characterized by intrauterine growth restriction, clenched hands, and low set ears

Trisomy 18

18

Single gene defects can interrupt

Specific organ development

19

Mutations in specific transcription factors can cause developmental disorders in overall body patterning or genesis of

Specific organs

20

A variety of teratogens (such as drugs) can affect development and lead to

Deformities

21

Act during critical times of organ formation

Teratogens

22

Nothing in weeks 1 and 2 of pregnancy is susceptible to

Teratogens

23

What is the most sensitive to teratogens throughout most of the pregnancy?

Central Nervous System

24

The risk of birth defects from many teratogens are highest during the

Embyonic Period (3-8 weeks)

25

Developed as sedative and insomnia treatment. However, if the fetus exposed at 24-36 days,
limb outgrowth is dramatically affected

-Does not effect subsequent digit development

Thalidomide

26

What are three major developmental signaling pathways?

-used at different steps in multiple tissues

1.) Transforming growth factor beta (TFG-β)
2.) Fibroblast growth factor (FGF)
3.) Retinoic Acid (RA)

27

A family of over 30 peptides that bind to serine-threonine kinase receptors

TGF-β

28

Made up of over 20 peptides that bind to tyrosine kinase receptors

FGF

29

Binds to nuclear receptors to regulate gene transcription, and has endogenous enzymatic control of its synthesis and degradation

Retinoic Acid (RA; derived from vitamin A)

30

Signal transduction via receptor kinases occurs when a ligand binds a receptor kinase in the cell exterior, causing a conformational change and phosphorylation cascade on the cell interior. Variations of this theme are used by

TGF-β and FGF pathways

31

Does not bind kinase receptors but instead binds nuclear receptors

-always located in the nucleus

Retinoic Acid

32

TGF-β ligands bind as a

Dimer

33

TGF-β binds to a type II receptor, which causes the receptor to recruit and phosphorylate a

Type I receptor

34

Phosphorylated type I receptor recruits and phosphorylates

Smad2 or Smad3

35

Phosphorylated Smad2 or Smad3 dissociates from the receptor and oligomerizes with

Smad4

36

Unfold when phosphorylated

Smads

37

Migrates to the nucleus, recruits other gene regulatory proteins, and activates transcription of specific target genes

Smad2(3)/Smad4 oligomer

38

Can antagonize action of the TGF-β peptide BMP-4 by binding to it and thus preventing BMP-4 dimer formation

Chordin, noggin, and lefty

39

What are the three TFG-like peptides we need to know

1.) TFG-β like (nodal)
2.) Mone morphogenetic proteins (BMP-4)
3.) Activins

40

Chordin, noggin, and lefty bind the BMP-4 monomer and prevent BMP-4 dimer formation by forming a dimer of their own, which can not bind/activate

BMP receptors

41

What are the four FGF receptors?

FGFR-1 through FGFR-4

42

Critical for early axis formation and for development of several organs, particularly bone and cartilage

FGFs

43

Helps present FGF to tyrosine kinase receptors and presumably helps stabilize the active dimeric receptor even though FGF is a monomer

Cell surface/transmembrane Heparin Sulfate

44

The inner cell mass (ICM) is the source of all

Embryonic tissues and stem cells

45

Changes in molecular identity of cells occur prior to organization of specific cell types in

Early embryonic Development

46

Early fetal lineages are already specified in a mixture of cells as noted by different transcription factor expression before they are sorted to

Different regions

47

This tissue will arise from the portion of the epiblast (blue) that is at the posterior end of the embryo via movement through the primitive streak

Mesoderm

48

Will form connective tissue and will control nervous system formation

Mesoderm

49

When does the primative streak form?

14 days in

50

The embryonic endoderm and mesoderm are derived from cells that enter the

Primative streak

51

First to enter embryo during gastrulation

Endodermal cells

52

Arise from the epiblast and enter the interior of the embryo, spread extensively, and give rise to dorsal and ventral derivatives

Mesoderm

53

What are some dorsal mesoderm derivatives?

Bone, cartilage, and muscle

54

What are some ventral mesoderm derivatives?

Kidney and blood

55

The area of active invagination into the inner embry

Node

56

A major determinant of mesoderm formation in the mammal

-mutation in mice caused a complete lack of mesoderm

The TGF-β peptide "nodal"

57

“Nodal” is expressed in posterior region of embryo called the

-where mesoderm will form

Node

58

Using the gene sequence of nodal as a probe, nodal expression was found in the

Primative streak

59

Acts to generally inhibit initial mesoderm and nervous system development

BMP-4

60

BMP-4 can be inhibited by the antagonists

Chordin, noggin, and lefty

61

Initially induced by nodal at an earlier stage, which then both limits nodal expression as well as contributes to anterior head structure formation

Anterior visceral endoderm (AVE)

62

“Nodal” expression begins even earlier and first induces another important region of the early embryo, which is called the

Anterior visceral endoderm (AVE)

63

The Anterior visceral endoderm (AVE) is required for differentiation of

Anterior Structures

64

Induced AVE in turn produces inhibitors that suppress nodal expression in most of embryo except for a small region at posterior end called the

Node

65

There, at the “node” region, nodal expression increases to the “threshold” level needed for mesoderm to form and for

Primative streak formation

66

Noggin and Chordin are produced at the

Node

67

A transcription factor that will allow anterior structures to be induced in mesoderm moving anterior

-Also produced at the node

Goosecoid

68

In addition to nodal, several other genes also affect mesoderm formation. One example of this is the T-box transcription factor

Brachyury

69

Knockout of brachyury in mice leads to deficient

Posterior mesoderm ("tail-less" phenotype)

70

Directs anterior mesoderm formation, which in turn directs head patterning

Goosecoid

71

Too much gooscoid can lead to

Conjoined twins

72

Sirenomelia defects reflect decreased posterior mesoderm and possibly result from too little

Chordin, Noggin, brachury, or FGF (or too much retinoic acid)

73

Expressed in the forming mesoderm and leads to the formation of right and left sides

FGF peptide FGF8

74

FGF in mesoderm promotes continued chordin and noggin expression, which in turn continue to inhibit

BMP-4

75

The inhibition of BMP-4, especially in the dorsal region, promotes more mesoderm production as well as neural tissue development from

Ectoderm

76

A major regulator of FGF is

Retinoic Acid (RA)

77

Endogenous RA is produced and normally active in only small areas of the embryo where it activates

Nuclear RA receptors RAR and RXR

78

Results in much reduced posterior structures and some transformation of posterior structures to anterior structures

Excess retinoic acid

79

A potent teratogen at very low doses

Retinoic acid

80

Despite this teratogenicity, 13-cis-retinoic acid is prescribed for

Acne (accutane)

81

Also teratogenic at very high concentrations (10,000 units/day) because it will alter in vivo retinoic acid levels

Vitamin A

82

Has reciprocal inhibitory actions with an FGF isoform

Retinoic acid

83

RAldh2 (synthetic RA enzyme) is present in somite-derived mesoderm and thus RA is made by somites adjacent to neural tube and released. This RA binds to RA receptors in “stem” zone containing

FGF expressing cells

84

Maintenance of posterior FGF is needed for the development of

Posterior structures

85

Gradually turns off FGF8 from rostral to caudal

RA

86

Since the body axis forms from rostral to caudal, RA gradually shuts off FGF8 in a tightly controlled manner that allows

Posterior structures to form

87

Needed to allow posterior structures to keep
forming normally, and if it is turned off prematurely, there will be deficits in these structures

FGF8

88

Excess RA will turn off

-results in posterior structure deficiencies

FGF8

89

Direct the development of posterior structures

5' Hox genes

90

Causes FGF to turn off prematurely. Thus activation of more 5’ genes in the Hox cluster will not proceed, and as a consequence, posterior mesoderm will be reduced

Excess RA

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