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MSK I > Review Primitive Pit, Prim Node, Prim Streak, their involvement in formation of primary germ layers > Flashcards

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

1
Q

Gastrulation =

A

formation of primary germ layers

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2
Q

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

A

epiblast cells: this is called invagination

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3
Q

Cell migration of epiblast cells during invagination requires

A

FGF8, transcription factor

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4
Q

FGF-8 is made by the

A

primitive streak

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5
Q

What does the epiblast migration do?

A

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

whatever remains is called the ectoderm

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6
Q

Body Axis is established

A

before and during gastrulation

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7
Q

Body Axis: Head formation is caused by

A

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

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8
Q

AVE does what

A

Anterior Visceral Endoderm

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

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9
Q

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

A

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

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10
Q

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

A

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

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11
Q

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

A

Nodal and Activin

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12
Q

Goosecoid, chordin, noggin and fallistatin do what

A

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

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13
Q

name a BMP-4 inhibitor

A

goosecoid, noggin, fallistatin, chordin

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14
Q

why is BMP-4 inhibition important

A

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

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15
Q

Goosecoide —>

A

BMP-4 inhibitor, thus BODY AXIS FORMATION

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16
Q

NODAL genes do what

A

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

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17
Q

Goosecoid overexpression —>

A

two headed animals (people, snakes etc)

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18
Q

Brachury (T) gene

A

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

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19
Q

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

A

primitive node, antagonize BMP-4

20
Q

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

A

cell migration. movement of cells from the primitive streak

21
Q

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

A

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

22
Q

Primitive Node —> (4 things)

A

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)

23
Q

Caudal dysgenesis

A

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

24
Q

Laterality (L/R Asymmetry) is the

A

“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

25
Q

Laterality is established by initial expression of

A

FGF-8 in the primitive node and streak

establishes Nodal on the LEFT side only (AFTER gastrulation)

26
Q

Nodal expression in laterality establishment

A

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

27
Q

what stimulates NODAL expression and on what side

A

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

28
Q

Laterality and Shh

A

Shh stimulates NODAL expression and inhibits Activin

29
Q

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

A

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

30
Q

Shh =

A

Nodal stimulation on the left

Inhibited by activin on the Right

31
Q

Shh is expressed on which side

A

both, it is bilateral

32
Q

PITX2

A

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

33
Q

Serotonin

A

5HT

important signaling molecule in establishing laterality

34
Q

disrupting 5HT does what

A

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)

35
Q

what is the signaling chain involving 5HT?

A

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

36
Q

MAO

A

monoamine oxidase (MAO)

metabolizes 5HT

37
Q

why are SSRIs dangerous in new mothers?

A

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

disrupts “left sidedness”

38
Q

Situs inversus =

A

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

39
Q

Dextrocardia

A

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

40
Q

difference between situs inversus and detrocardia

A

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

41
Q

Heterotaxy

A

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

42
Q

“Nodal Flow”

A

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

43
Q

Nodal Flow basics

A

cilia create a leftward flow of nodal flow toward the left which initiates L-R symmetry

(remember, 5HT –> FGF8–> NODAL/Lefty2 –> PITX2 = Left sidedness)

44
Q

Kartengener syndrome

A

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

45
Q

Genes involved in Right Sided development

A

Not well defined. Zinc finger transcription factor SNAIL is restricted to the Right side

snail transcription is repressed by nodal

46
Q

Snail transcription is repressed by

A

nodal signaling

MSK I (14 decks)

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