Early Vert Development (6) Flashcards
When are the A/V and D/V axis determined?
- early on
Where is there asymmetry in the adult body?
- with the positions of organs in the body
- ex. heart more towards the left side
- with chirality
- ex. coiling of tissue/organ in clockwise versus counterclockwise manner
What is situs?
- position (in the body)
What is situs solitus?
- the normal disposition of organs
What is situs inversus?
- defect or abnormality that can happen with other organs
- organ is ‘flipped’ to wrong side
What are some names of defects?
- situs inversus totalis
- left isomerism (polysplenia)
- right isomerism (asplenia)
- situs inversus abdominalis
- situs inversus thoracalis
What is situs inversus totalis?
- all organs are ‘flipped’ or mirror imaged
What is left isomerism and right isomerism?
- when right side mirrors the left side (like two left sides)
- same for right
What is situs inversus abdominalis? Situs inversus thoracalis?
- the abdominal region is flipped
- the thoracic region is flipped (lung and heart)
What are symptoms of laterality disorders in humans?
- viable but more vulnerable to certain diseases or conditions
- frequently associated with organ malformations and/or functional disorders
What is situs ambiguus?
- anything deviating from situs solitus
What conditions are associated with situs ambiguus?
- complex cardiovascular malformations
- anomalies of the spleen and gastrointestinal system
- over 80% of children present with complex congenital heart disease
How is left right asymmetry established during development?
- correlative evidence underlying left right asymmetry trace back to the node
- nodal pit separates left and right side
Where is nodal expressed?
- using in situ hybridization
- expressed “peri-nodal” (not in node but around it) at 7.5 days
- at 8 days, more pronounced on left side
- left right asymmetry of nodal
What family is nodal in? What is it related to?
- TGF-B family
- related to Lefty which is also a TGF-B family member)
What is KIF3B?
- microtubule motor protein (kinesin family member)
What happens in a KIF3B mutant?
- in KIF3B null mice, lefty is no longer expressed asymmetrically on left side
- cilia are lost in the node
What experiment was conducted to test if cilia in the node are important for left-right asymmetry?
- Nonaka
- visualized nodal cilia by dissecting embryo out and putting node on microscope slide with media
- used light microscopy to visualize
- see cilia moving in clockwise circles (when viewed from ventral side)
What experiment was done to see if the cilia generate a current?
- use fluorescent beads to see where they travel
- travel from right to left
- generates/establishes asymmetry
What experiment was conducted to see if cilia current contributes to left-right asymmetry?
- create an artificial current and use beads to see if overall current changes, then observe effects on asymmetry
- with fast current from left to right, the asymmetry is flipped
It appears the flow is important for asymmetry, but what is the actual purpose of the flow?
- could be signalling molecule being released and transported
- could be physical/mechanical force to stimulate peripheral cilia (like hair cells)
- both would activate intracellular signalling cascades and gene transcription
- there are factors in the node but could be a combination of the two above
What is Pitx2?
- transgene reporter expression within the heart
- used to visualize heart development
What is CAC and TA?
- common atrium chamber
- truncus arteriosus
- examined for reversed or normal asymmetry
What is the role of nodal in signalling left-right asymmetry?
- nodal loss led to left-right patterning defects
- sonic hedgehog activated the cerberus homologue caronte
- caronte inhibits BMP which stops BMP from inhibiting Nodal
- Nodal is able to activate transcription factor PITX2 (in the left side)
