title: Cadherin-9 regulates synapse-specific differentiation in the developing hippocampus.
abstract: Our understanding of mechanisms that regulate the differentiation of specific classes of synapses is limited. Here, we investigate the formation of synapses between hippocampal dentate gyrus (DG) neurons and their target CA3 neurons and find that DG neurons preferentially form synapses with CA3 rather than DG or CA1 neurons in culture, suggesting that specific interactions between DG and CA3 neurons drive synapse formation. Cadherin-9 is expressed selectively in DG and CA3 neurons, and downregulation of cadherin-9 in CA3 neurons leads to a selective decrease in the number and size of DG synapses onto CA3 neurons. In addition, loss of cadherin-9 from DG or CA3 neurons in vivo leads to striking defects in the formation and differentiation of the DG-CA3 mossy fiber synapse. These observations indicate that cadherin-9 bidirectionally regulates DG-CA3 synapse development and highlight the critical role of differentially expressed molecular cues in establishing specific connections in the mammalian brain.
authors.affiliation: Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0366, USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Williams
authors.forename: Scott A
authors.initials: SA
authors.lastname: Wilke
authors.forename: Anthony
authors.initials: A
authors.lastname: Daggett
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Davis
authors.forename: Stefanie
authors.initials: S
authors.lastname: Otto
authors.forename: Deepak
authors.initials: D
authors.lastname: Ravi
authors.forename: Beth
authors.initials: B
authors.lastname: Ripley
authors.forename: Eric A
authors.initials: EA
authors.lastname: Bushong
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ellisman
authors.forename: Gerd
authors.initials: G
authors.lastname: Klein
authors.forename: Anirvan
authors.initials: A
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D006624:Hippocampus / Q000033:anatomy & histology* / Q000254:growth & development* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure*; D018408:Patch-Clamp Techniques; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D015415:Biomarkers; D015820:Cadherins; C561947:cadherin-9, mouse