Genetic and Environmental Influences on Early Human Development

Question 1

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

Answer 1

1/3

Question 2

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

Answer 2

Congenital malformations (present at birth)

Question 3

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

Answer 3

20%

Question 4

The field that has emerged to study abnormal development in embryos

-investigates the causes of congenital abnormalities/birth defects

Answer 4

Teratology

Question 5

7% of congenital abnormalities are known to be caused by

-can be chemical toxins, infections, or maternal deficiency

Answer 5

Teratogenic agents

Question 6

Will often kill embryo in first two prenatal weeks or lead

to spontaneous abortions in the first 6-8 weeks of gestation

Answer 6

Teratogenic agents

Question 7

Teratogens can cause organ-specific abnormalities from days

Answer 7

15-60

Question 8

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

Answer 8

5-15%

Question 9

Most cases of Down syndrome are caused by a deficit in

-produces gamete with 2 copies of chromosome 21

Answer 9

Meiosis I

Question 10

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

-No symptoms

Answer 10

Robertsonian translocation

Question 11

Has the symptoms of distinct facial features, congenital

heart disease, mental and growth retardation

Answer 11

Down Syndrome

Question 12

Almost all alterations in chromosome number will be lethal in

Answer 12

Early embryo

Question 13

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

Answer 13

Trisomy 13 and trisomy 18

Question 14

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

Answer 14

Midline defects

Question 15

Cleft lip and palate and CNS malformations are characteristic of

Answer 15

Trisomy 13

Question 16

Tend to survive longer with trisomy 18

Answer 16

Females

Question 17

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

Answer 17

Trisomy 18

Question 18

Single gene defects can interrupt

Answer 18

Specific organ development

Question 19

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

Answer 19

Specific organs

Question 20

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

Answer 20

Deformities

Question 21

Act during critical times of organ formation

Answer 21

Teratogens

Question 22

Nothing in weeks 1 and 2 of pregnancy is susceptible to

Answer 22

Teratogens

Question 23

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

Answer 23

Central Nervous System

Question 24

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

Answer 24

Embyonic Period (3-8 weeks)

Question 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

Answer 25

Thalidomide

Question 26

What are three major developmental signaling pathways? -used at different steps in multiple tissues

Answer 26

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

Question 27

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

Answer 27

TGF-β

Question 28

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

Answer 28

FGF

Question 29

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

Answer 29

Retinoic Acid (RA; derived from vitamin A)

Question 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

Answer 30

TGF-β and FGF pathways

Question 31

Does not bind kinase receptors but instead binds nuclear receptors -always located in the nucleus

Answer 31

Retinoic Acid

Question 32

TGF-β ligands bind as a

Answer 32

Dimer

Question 33

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

Answer 33

Type I receptor

Question 34

Phosphorylated type I receptor recruits and phosphorylates

Answer 34

Smad2 or Smad3

Question 35

Phosphorylated Smad2 or Smad3 dissociates from the receptor and oligomerizes with

Answer 35

Smad4

Question 36

Unfold when phosphorylated

Answer 36

Smads

Question 37

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

Answer 37

Smad2(3)/Smad4 oligomer

Question 38

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

Answer 38

Chordin, noggin, and lefty

Question 39

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

Answer 39

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

Question 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

Answer 40

BMP receptors

Question 41

What are the four FGF receptors?

Answer 41

FGFR-1 through FGFR-4

Question 42

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

Answer 42

FGFs

Question 43

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

Answer 43

Cell surface/transmembrane Heparin Sulfate

Question 44

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

Answer 44

Embryonic tissues and stem cells

Question 45

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

Answer 45

Early embryonic Development

Question 46

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

Answer 46

Different regions

Question 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

Answer 47

Mesoderm

Question 48

Will form connective tissue and will control nervous system formation

Answer 48

Mesoderm

Question 49

When does the primative streak form?

Answer 49

14 days in

Question 50

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

Answer 50

Primative streak

Question 51

First to enter embryo during gastrulation

Answer 51

Endodermal cells

Question 52

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

Answer 52

Mesoderm

Question 53

What are some dorsal mesoderm derivatives?

Answer 53

Bone, cartilage, and muscle

Question 54

What are some ventral mesoderm derivatives?

Answer 54

Kidney and blood

Question 55

The area of active invagination into the inner embry

Answer 55

Node

Question 56

A major determinant of mesoderm formation in the mammal -mutation in mice caused a complete lack of mesoderm

Answer 56

The TGF-β peptide "nodal"

Question 57

“Nodal” is expressed in posterior region of embryo called the -where mesoderm will form

Answer 57

Node

Question 58

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

Answer 58

Primative streak

Question 59

Acts to generally inhibit initial mesoderm and nervous system development

Answer 59

BMP-4

Question 60

BMP-4 can be inhibited by the antagonists

Answer 60

Chordin, noggin, and lefty

Question 61

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

Answer 61

Anterior visceral endoderm (AVE)

Question 62

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

Answer 62

Anterior visceral endoderm (AVE)

Question 63

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

Answer 63

Anterior Structures

Question 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

Answer 64

Node

Question 65

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

Answer 65

Primative streak formation

Question 66

Noggin and Chordin are produced at the

Answer 66

Node

Question 67

A transcription factor that will allow anterior structures to be induced in mesoderm moving anterior -Also produced at the node

Answer 67

Goosecoid

Question 68

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

Answer 68

Brachyury

Question 69

Knockout of brachyury in mice leads to deficient

Answer 69

Posterior mesoderm ("tail-less" phenotype)

Question 70

Directs anterior mesoderm formation, which in turn directs head patterning

Answer 70

Goosecoid

Question 71

Too much gooscoid can lead to

Answer 71

Conjoined twins

Question 72

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

Answer 72

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

Question 73

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

Answer 73

FGF peptide FGF8

Question 74

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

Answer 74

BMP-4

Question 75

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

Answer 75

Ectoderm

Question 76

A major regulator of FGF is

Answer 76

Retinoic Acid (RA)

Question 77

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

Answer 77

Nuclear RA receptors RAR and RXR

Question 78

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

Answer 78

Excess retinoic acid

Question 79

A potent teratogen at very low doses

Answer 79

Retinoic acid

Question 80

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

Answer 80

Acne (accutane)

Question 81

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

Answer 81

Vitamin A

Question 82

Has reciprocal inhibitory actions with an FGF isoform

Answer 82

Retinoic acid

Question 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

Answer 83

FGF expressing cells

Question 84

Maintenance of posterior FGF is needed for the development of

Answer 84

Posterior structures

Question 85

Gradually turns off FGF8 from rostral to caudal

Answer 85

RA

Question 86

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

Answer 86

Posterior structures to form

Question 87

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

Answer 87

FGF8

Question 88

Excess RA will turn off -results in posterior structure deficiencies

Answer 88

FGF8

Question 89

Direct the development of posterior structures

Answer 89

5' Hox genes

Question 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

Answer 90

Excess RA