Left- Right asymmetry Flashcards
in which phylogenetic group is the nodal pathway found in?
deuterosomes and protosomes
in which protostomes has the nodal pathway ben described ?
he mollusks
what have gain an loss of function mutations revealed about the role of Nodal in the mollusk?
it is needed for shell coiling i.e asymmetrical organ placement
what form of left right asymmetry are there in the c.elegan?
rotates in the egg shell, lateralisation of the nervous system
what is an asymmetry in the fly?
the gut rotates asymmetrically
what is the evidence for the nodal pathway role in c.elegans and flies?
no nodal homologues have been found after the genome sequencing
how does asymmetric induction of nodal occur in the snail?
- chiral blastomere arrangement at the 8 cell stage
what evidence is there in xenopus for the early asymmetry?
the first cleavage division is inherently chiral
what is the left right organiser in the fish?
kupffer’s vesicle
what is the left right organiser in the xenopus?
gastrocoel roof plate
what is the mouse LR organiser?
the node
have cilia been implicated in the chick
?
no
where is asymmetry first found in the mouse?
at the node and then transferred to the lateral plate mesoderm in the form of Nodal expression in the lateral plate mesoderm
what is thought to be the symmetry breaking step in the mouse?
the leftward movement across the node
where on the node are the cilia found?
protrude from cells located on the ventral side of the node into the node cavity
what direction so the cilia beat in?
clockwise
the node when does flow exist?
2 until 4 somite stage
what is the phenotype of the inversus visceral mouee mutant and what is this mutant?
- immotile cilia- randomised LR orientation
how is the flow in the mouse shown to be the determining feature?
when you apply a synthetic flow in a mutant then you swap the side of LR
what is the phenotype of fish that lack cilia in their Kuppfer’s vesicle?
LR defects
how do the cilia of the mouse node rely on the other axis? how does this link with the initial theory of LR?
The AP axis influences the tilt of the node cilia, whereas the DV axis is represented by their ventral protrusion. The origin of the LR axis is thus, indeed, dependent on AP and DV positional information. The node cilium thus corresponds to the hypothetical F-molecule
hat is thought to stimulate the posterior tilt of the cilia?
the PCP pathway
in the determinant transport theory of the mouse, where would the factored to be secreted from?
by the node cells- the pit cells
what is wrong with the factor movement theory in the mouse?
the identity of the cells which detect the determinant is unknown
- no suitable candidate has been found
why is shh not a good candidate for the factor transport theory?
Shh–/– embryos show left isomerism as a result of impaired midline function. The LR decision is initially normal in the Shh-null embryos, but they subsequently develop bilateral Nodal expression in the lateral plate because of the midline abnormality
why is retinoic acid not a good candidate for the nodal flow mouse theory?
- KO of the enzyme which makes it results in normal LR
what is the mechanical stress theory in the mouse?
that nodal flow transports an LR determinant is that it generates mechanical stress that is sensed by node cells, either pit cells or crown cells (the cells around the node)
why was Ca2+ signalling first implicated in LR in the mouse?
Ca2+ signalling has been detected at the left margin of th node
what is the role of the calcium channel in mouse LR?
PKD2 encodes a Ca2+ release channel Pkd2 mutant mice develop LR defects that are consistent with impaired mechanosensation. They, thus, possess morphologically normal and motile cilia but fail to develop asymmetric expression of Nodal in the LPM.
Recent observations support the notion that Pkd2 acts as a Ca2+ channel that is gated by mechanical stress
what is the phenotype of a PDK2 mutant mouse? (2)
Pkd2 mutant mice develop LR defects that are consistent with impaired mechanosensation. They, thus, possess morphologically normal and motile cilia but fail to develop asymmetric expression of Nodal in the LPM
- Pkd2–/– embryos do not manifest asymmetric Ca2+ signaling in the perinodal endoderm
scribe the pattern of expression on the left side of the mouse?
- nodal expressed on the left side of the node
- nodal expressed int he lateral plate mesoderm
- lefty2 is expressed in the lateral plate mesoderm
- lefty 1 negatively regulates nodal at the midline
what is the relationship between the expression of nodal in the node and in the lateral plate mesoderm?
- it is needed for the second
what is a thought bout how nodal gets from the node to the LPM?
may be transferred and activate itself
- may induce something in between which activate Nodal
in the absence of nodal, what happens to the right?
takes on left isomerism
why is lefty 1 and 2 important ?
In the absence of Lefty1 or Lefty2, asymmetric Nodal expression in the LPM begins normally, but the Nodal signal subsequently leaks to the right side, resulting in bilateral Nodal expression
is it known how LR nodal confers organ asymmetry?
no
in which vertebrate has fluid flow not been implicated in?
the pig and the chick
where is pitx2 found?
on the left of vertebrates
what asymmetry is found in xenons before the nodal flow?
- the segregation of H+ and K+ ATPase mRNA and protein in one cell more than the other
how is the asymmetry of the K+and H+ aptness mRNA thought to accumulate on one side more than the other in the 2 cell stage?
probably involve unidirectional transport by a motor protein along the cytoskeleton. In addition, directionality of the embryonic cytoskeleton itself, that is the position of the ‘+’ ends and ‘–’ ends, might play a role in moving the motor protein in one direction
he asymmetry of what has been linked with the asymmetry of H+ and K+ ATPase mRNA in the xenopus?
serotonin
what has been found so far about LR in the chick?
asymmetric cell migration around the LR organizer is an early event that has been observed in birds resulting in the generation of asymmetric gene expression around this structure. this requires H+/K+ ATPase.H+/K+-ATPase is also indispensable for left- right asymmetry in Xenopus and chick. In the chick, asymmetric localization of H+/K+-ATPase mRNA is apparent at Hensen’s node and is required for the subsequent establishment of Sonic hedgehog (Shh) asymmetric gene expression
what two types of cilia have been found in the mouse and what is the significance of this?
motile and immoltie- the immotile thought to sense the mechanal force of the flow
what is the state of flow within the gastroceol roof plate?
In Xenopus, fluid flow is necessary only in the left portion of the GRP (Vick et al., 2009), suggesting that the cells on the left side of this structure sense the signal, whether it be mechanical or chemical
what is the state of flow within the zebrafish ?
motile cilia are present at the ventral and dorsal surface inside this vesicle, but they are preferentially found in the anterior region of KV. Although cilia in the anterior region are posteriorly tilted, the basal body is not significantly shifted towards the posterior side. Nonetheless, unidirectional flow (counterclockwise as observed from the dorsal side) is formed in the anterior-dorsal region of KV
how is the role of PCP conserved?
The posterior localization of the basal body within node cells can be regarded as a type of planar cell polarity (PCP) and is regulated by the noncanonical Wnt signaling pathway in the mouse and Xenopus, and in zebrafish, the distribution of cilia inside KV is also regulated
how is calcium signalling the mouse linked to the fish?
and Ca2+/calmodulin- dependent kinase II (CamKII) is required in KV for LR patterning
how does LR asymmetry occur in c.elegans?
asymmetrical cleavage involving notch: signaling between the AB and MS descendents, again utilizing GLP-1, produces distinct lineages on the left and right sides
