Review Primitive Pit, Prim Node, Prim Streak, their involvement in formation of primary germ layers Flashcards
Gastrulation =
formation of primary germ layers
What cells move TO the primitive streak and then through the primitive groove?
epiblast cells: this is called invagination
Cell migration of epiblast cells during invagination requires
FGF8, transcription factor
FGF-8 is made by the
primitive streak
What does the epiblast migration do?
displaces hypoblast cells to become ENDODERM, cells also form a middle layer called the MESODERM
whatever remains is called the ectoderm
Body Axis is established
before and during gastrulation
Body Axis: Head formation is caused by
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
AVE does what
Anterior Visceral Endoderm
expresses cerberus and Lefty the cranial end of embryo
essential in body axis development
There are “4” signaling chain reactions leading to the development of the notochord and paraxial mesoderm
Goosecoid transcription factor –> Chordin/Noggin/Follistatin –> INHIBITION OF BMP —> formation of DORSAL mesoderm —> Notochord + Paraxial mesoderm
There are “3” signaling events leading to the formation of lateral and intermediate mesoderm
(BMP-4) combines with FGF —> formation of VENTRAL mesoderm –> Lateral and Intermediate mesoderm development
The primitive streak is “initiated and maintained” by what secretory proteins encoded by the NODAL gene?
Nodal and Activin
Goosecoid, chordin, noggin and fallistatin do what
inhibit BMP, thus inhibit ventral mesoderm formation, thus allowing dorsal mesoderm formation
name a BMP-4 inhibitor
goosecoid, noggin, fallistatin, chordin
why is BMP-4 inhibition important
it allows dorsal mesoderm developing, which allows for notochord and paraxial mesoderm to develop
Goosecoide —>
BMP-4 inhibitor, thus BODY AXIS FORMATION
NODAL genes do what
they upregulate Nodal and activin. NODAL is responsible for dorsal/ventral mesoderm formation
Goosecoid overexpression —>
two headed animals (people, snakes etc)
Brachury (T) gene
regulates dorsal mesoderm formation in the middle and caudal regions of embry
Brachury (T) gene expressed in the ___ and does what?
primitive node, antagonize BMP-4
what “overall” is brachury T gene expression required for?
cell migration. movement of cells from the primitive streak
Nodal —> Goosecoid —> _____ —> _______ mesoderm into ______ and _________ for the ______
inhibition of BMP-4 –> dorsal mesoderm into notochord and paraxial mesoderm for the head region
Primitive Node —> (4 things)
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)
Caudal dysgenesis
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
Laterality (L/R Asymmetry) is the
“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
Laterality is established by initial expression of
FGF-8 in the primitive node and streak
establishes Nodal on the LEFT side only (AFTER gastrulation)
Nodal expression in laterality establishment
It’s expressed symetrically early on; during the second phase, it’s secreted by primitive streak and node on the left side only
what stimulates NODAL expression and on what side
FGF-8 stimulates it from p. node and p. streak, expressed on the left
Laterality and Shh
Shh stimulates NODAL expression and inhibits Activin
For nodal to be expressed on the LEFT, avtivin does what
inhibits Shh expression on the RIGHT by inhibiting Shh’s stimulating effects on NODAL
Shh =
Nodal stimulation on the left
Inhibited by activin on the Right
Shh is expressed on which side
both, it is bilateral
PITX2
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
Serotonin
5HT
important signaling molecule in establishing laterality
disrupting 5HT does what
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)
what is the signaling chain involving 5HT?
5HT –> FGF8 –> LODAL/LEFTY2 –> PITX2 (Pitx2 is important in asymmetry)
MAO
monoamine oxidase (MAO)
metabolizes 5HT
why are SSRIs dangerous in new mothers?
they disrupt 5HT which is critical in the expression of PITX2, responsible for asymmetrical development of organs on the left
disrupts “left sidedness”
Situs inversus =
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
Dextrocardia
liver ends up right, stomach ends up left with the spleen
difference between situs inversus and detrocardia
situs inversus is switching thoracic organs, dextrocardia switches spleen, stomach, and liver around
Heterotaxy
an unusual anatomical arrangement inside the body. visually it is exhibited by a high degree of symmetry. includes patients with complex cardiac lesions.
“Nodal Flow”
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
Nodal Flow basics
cilia create a leftward flow of nodal flow toward the left which initiates L-R symmetry
(remember, 5HT –> FGF8–> NODAL/Lefty2 –> PITX2 = Left sidedness)
Kartengener syndrome
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
Genes involved in Right Sided development
Not well defined. Zinc finger transcription factor SNAIL is restricted to the Right side
snail transcription is repressed by nodal
Snail transcription is repressed by
nodal signaling
