Journal Club: 10/06/14
Type II Cadherins drive assembly of direction selectivity
- presented by Colesno
- Saines lab, Cell paper
- how do all these different cells wire up?
- On-off direction selective ganglion cells
- get inputs from on and off bipolar cells in distinct innerplexiform layers
- cell type specific promoters to drive expression particularly in Off bipolar cells and On biopolar cells separately.
- drive channel rhodopsin in these ON and OFF cells, show that they make synaptic connections to the ganglion cells. two photon single cell stimulation
- what molecules guide axon targeting?
- type 2 biopolars never go deep, type 5 never go to shallow layers
- focus in this paper on cadherins.
- family of 100+ genes in human/mouse.
- mediate adhesive cell connections. Mostly homotypically. Some cis and some trans interactions (within and between cells).
- some expression patterns of cadherins
- take promoters of these different cadherins and generate different Bipolar Cell specific expression.
- some Bipolar cell types uniquely express Cadh8, others (type 5) uniquely express Cadh9
- knockout the Cadh8/9 the type 2 5 cells now form connections to both layers.
- in mouse axons go in (semipromiscuously) and trim back (from this presumably based on contact).
- ectopic overexpression of the different cadherins is sufficient to target synapses to the opposite layer.
- this even works in different, non-bipolar cell types.
- visual responses are abnormal in these mutants. knock out cad8, diminished off response. knock out cad9, lose completely the On response.
- how many neurons specifically express particular cadherins (or other adhesion molecules)?
- Do the contact cells express the same cadherin?
- these are heterophilic expression – don’t depend on cad9 (can knock cad9 out globally).
- why just these two layers? (something pre-patterned).
- how do you chose the right cell once you get to the right layer? (other molecules? IgSF?)
- related to combinatoric DsKam neuroselection
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