left/right assymetry Flashcards
give some examples of organs that display left/right asymmetry
heart, spleen, liver, gut, lung lobes, brain
when left/right asymmetry is correct what is this called
situs solitus
what is the inverse of situs solitus and how many people are affected?
situs invertus
1/10,000
which organ develops in the midline and then moves to the left side and loops to the right?
the heart
what does tbx5 mutation cause?
stronger limb malformation on the left hand side
name a ventricle signal in the developing embryo
Shh
name three genes that are expressed only in L or R side of embryo?
Shh
FGF
nodal
how is L/R asymmetry made in organogenesis?
- directional looping
- increased proliferation
- regulated branching
- cell death
describe two past theories of what causes L/R assymetry
- electric/magnetic fields
- chiral molecules
what causes Kartagener syndrome?
immotile cilia
name 3 symptoms of Kartagener syndrome
- chronic respiratory infection
- male infertility
- situs invertus in 50% of cases
what was suggested about L/R asymmetry from the finding of Kartagener syndrome
that cilia are involved in the development of L/R asymmetry
what was observed in some situs invertus mice?
dynein motor protein defects (involved in cilia movement)
why does a combination of situs solitus and situs invertus lead to problem?
organs do not fit together well and can crush each other
what is the node called in chicks (where it was discovered)
Hensen’s node
what is the node
a major conserved signalling centre essential for gastrulation
what does each cell of the node have?
a single cilia of the 9+0 class
what is the 9+0 class cilia made up of?
dynein arms on 9 microtubule doublets
are cilia chiral?
yes
what does KIF stand for?
kinesin like protein
what was observed in KIF3-A and KIF3-B knock out mice? and what was different about their nodes?
randomised organ L/R asymmetry
nodes displayed no cilia
are nodal cilia motile?
yes, they create a nodal flow towards the left
where are the cilia located and what signalling causes this?
cilia are on the posterior end of the node cell
Wnt planar cell polarity signalling causes this
what is special about the cilia positioning?
they don’t interfere with each other or produce turbulence
what was observed when cilia removed from nodes and artificial rightward flow induced?
situs invertus
what causes polycystic kidney disease?
mutation in Pkd2 (polycystin 2), a calcium channel associated with mechanosensing cilia
what is are the symptoms of polycystic kidney disease?
enlarged kidneys full of cysts
does the node also have mechanosensing cilia?
yes, located on specific regions of node
what are mechanosensing cilia?
cilia that respond to bending with a calcium influx through Pkd2
what do Pkd2 mutants show?
L/R asymmetry defects
how does nodal flow affect L/R asymmetry?
bending of mechanosensing cilia leads to influx in calcium on the left hand side
this leads to activation of left handed genes
name three left bias genes in the nodal area? what happens to these if mutated in mice?
Nodal, lefty and PitX
mid-gestational death
how many people are left handed?
1/9
what occurs in Kartagener syndrome and what does it suggest?
situs invertus in all organs than the brain
suggests an independent mechanism for brain asymmetry
how is L/R asymmetry achieved in chicks? and what happens if this is disrupted?
only R eye see light
if chicks develop in dark then there is no asymmetry
why is the brain asymmetrical?
to allow us to parallel process/multi-task
