Review Primitive Pit, Prim Node, Prim Streak, their involvement in formation of primary germ layers

Question 1

Gastrulation =

Answer 1

formation of primary germ layers

Question 2

What cells move TO the primitive streak and then through the primitive groove?

Answer 2

epiblast cells: this is called invagination

Question 3

Cell migration of epiblast cells during invagination requires

Answer 3

FGF8, transcription factor

Question 4

FGF-8 is made by the

Answer 4

primitive streak

Question 5

What does the epiblast migration do?

Answer 5

displaces hypoblast cells to become ENDODERM, cells also form a middle layer called the MESODERM

whatever remains is called the ectoderm

Question 6

Body Axis is established

Answer 6

before and during gastrulation

Question 7

Body Axis: Head formation is caused by

Answer 7

expression of transcription factors CERBERUS + Lefty (and others) from the Anterior visceral endoderm (AVE)

what this does is block expression of NODAL in the region that WONT become the head

Question 8

AVE does what

Answer 8

Anterior Visceral Endoderm

expresses cerberus and Lefty the cranial end of embryo
essential in body axis development

Question 9

There are “4” signaling chain reactions leading to the development of the notochord and paraxial mesoderm

Answer 9

Goosecoid transcription factor –> Chordin/Noggin/Follistatin –> INHIBITION OF BMP —> formation of DORSAL mesoderm —> Notochord + Paraxial mesoderm

Question 10

There are “3” signaling events leading to the formation of lateral and intermediate mesoderm

Answer 10

(BMP-4) combines with FGF —> formation of VENTRAL mesoderm –> Lateral and Intermediate mesoderm development

Question 11

The primitive streak is “initiated and maintained” by what secretory proteins encoded by the NODAL gene?

Answer 11

Nodal and Activin

Question 12

Goosecoid, chordin, noggin and fallistatin do what

Answer 12

inhibit BMP, thus inhibit ventral mesoderm formation, thus allowing dorsal mesoderm formation

Question 13

name a BMP-4 inhibitor

Answer 13

goosecoid, noggin, fallistatin, chordin

Question 14

why is BMP-4 inhibition important

Answer 14

it allows dorsal mesoderm developing, which allows for notochord and paraxial mesoderm to develop

Question 15

Goosecoide —>

Answer 15

BMP-4 inhibitor, thus BODY AXIS FORMATION

Question 16

NODAL genes do what

Answer 16

they upregulate Nodal and activin. NODAL is responsible for dorsal/ventral mesoderm formation

Question 17

Goosecoid overexpression —>

Answer 17

two headed animals (people, snakes etc)

Question 18

Brachury (T) gene

Answer 18

regulates dorsal mesoderm formation in the middle and caudal regions of embry

Question 19

Brachury (T) gene expressed in the ___ and does what?

Answer 19

primitive node, antagonize BMP-4

Question 20

what “overall” is brachury T gene expression required for?

Answer 20

cell migration. movement of cells from the primitive streak

Question 21

Nodal —> Goosecoid —> _____ —> _______ mesoderm into ______ and _________ for the ______

Answer 21

inhibition of BMP-4 –> dorsal mesoderm into notochord and paraxial mesoderm for the head region

Question 22

Primitive Node —> (4 things)

Answer 22

Gooscoid - body axis formation
Nodal – primitive streak formation
T gene –movement of cells FROM the primitive streak (Brachyury (T) gene)
HNF-3beta (formation of notochord)

Question 23

Caudal dysgenesis

Answer 23

absence of brachury gene product resulting in shortening of embryo

degree depends on the time at which the protein became deficient

caudal regression syndrome, sacral agenesis, sirenomelia

Question 24

Laterality (L/R Asymmetry) is the

Answer 24

“second” critical event in in patterning of embryo after the “AP-Caudal/Cephalad” axis is formed

important in developing the asymmetry of the viscera

determined by several genes

Question 25

Laterality is established by initial expression of

Answer 25

FGF-8 in the primitive node and streak establishes Nodal on the LEFT side only (AFTER gastrulation)

Question 26

Nodal expression in laterality establishment

Answer 26

It's expressed symetrically early on; during the second phase, it's secreted by primitive streak and node on the left side only

Question 27

what stimulates NODAL expression and on what side

Answer 27

FGF-8 stimulates it from p. node and p. streak, expressed on the left

Question 28

Laterality and Shh

Answer 28

Shh stimulates NODAL expression and inhibits Activin

Question 29

For nodal to be expressed on the LEFT, avtivin does what

Answer 29

inhibits Shh expression on the RIGHT by inhibiting Shh's stimulating effects on NODAL

Question 30

Shh =

Answer 30

Nodal stimulation on the left | Inhibited by activin on the Right

Question 31

Shh is expressed on which side

Answer 31

both, it is bilateral

Question 32

PITX2

Answer 32

LEFT side of viscera homeobox containing transcription factor that is responsible for establishing left sidedness. will be expressed in the left side of the heart, stomach, primitive gut tube this helps establish asymmetry

Question 33

Serotonin

Answer 33

5HT important signaling molecule in establishing laterality

Question 34

disrupting 5HT does what

Answer 34

5HT = serotonin disruption can cause situs inversus dextrocardia and heart defects increase in congenital heart defects in children born to mothers who take antidepressants from selective serotonin reuptake inhibitors (SSRIs)

Question 35

what is the signaling chain involving 5HT?

Answer 35

5HT --> FGF8 --> LODAL/LEFTY2 --> PITX2 (Pitx2 is important in asymmetry)

Question 36

MAO

Answer 36

monoamine oxidase (MAO) metabolizes 5HT

Question 37

why are SSRIs dangerous in new mothers?

Answer 37

they disrupt 5HT which is critical in the expression of PITX2, responsible for asymmetrical development of organs on the left disrupts "left sidedness"

Question 38

Situs inversus =

Answer 38

left/right symm in heart reversed Left lung ends up with 3 lobes instead of 2 Right lung ends up with 2 lobes instead of 3 non fatal

Question 39

Dextrocardia

Answer 39

liver ends up right, stomach ends up left with the spleen

Question 40

difference between situs inversus and detrocardia

Answer 40

situs inversus is switching thoracic organs, dextrocardia switches spleen, stomach, and liver around

Question 41

Heterotaxy

Answer 41

an unusual anatomical arrangement inside the body. visually it is exhibited by a high degree of symmetry. includes patients with complex cardiac lesions.

Question 42

"Nodal Flow"

Answer 42

Leftward flow of extraembryonic fluid driven by rotatory movement of cilia that differentiate on the nodal cells, triggering the onset of L/R gene expression

Question 43

Nodal Flow basics

Answer 43

cilia create a leftward flow of nodal flow toward the left which initiates L-R symmetry (remember, 5HT --> FGF8--> NODAL/Lefty2 --> PITX2 = Left sidedness)

Question 44

Kartengener syndrome

Answer 44

problems with nodal flow: primary ciliary dyskinesia or immotile cilia syndrome autosomal recessive leads to at least 50% situs inversus symptoms include respiratory dysfunction, repeated respiratory infections, and infertility in men

Question 45

Genes involved in Right Sided development

Answer 45

Not well defined. Zinc finger transcription factor SNAIL is restricted to the Right side snail transcription is repressed by nodal

Question 46

Snail transcription is repressed by

Answer 46

nodal signaling