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