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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