title: Dapper Antagonist of Catenin-1 (Dact1) contributes to dendrite arborization in forebrain cortical interneurons.
abstract: In mice, genetically engineered knockout of the Dapper Antagonist of Catenin-1 (Dact1) locus, which encodes a scaffold protein involved in Wnt signaling, leads to decreased excitatory input formation on dendrites of developing forebrain neurons. We have previously demonstrated this in both (excitatory, glutamatergic) pyramidal neurons of the hippocampus and in (inhibitory GABAergic) interneurons of the cortex. We have also demonstrated that knockout of the Dact1 locus leads to decreased dendrite complexity in cultured hippocampal pyramidal neurons, and to decreased spine formation on dendrites of forebrain pyramidal neurons in vitro and in vivo. Synapse phenotypes resulting from Dact1 loss in cultured cortical interneurons can be rescued by recombinant overexpression of the Dact1 binding partner, Dishevelled-1 (Dvl1), but not by recombinant expression of a constitutively active form of the small GTPase Rac1. This contrasts with dendrite spine phenotypes resulting from Dact1 loss in cultured hippocampal pyramidal neurons, which can be fully rescued by recombinant expression of activated Rac1. Taken together, these data suggest that in maturing forebrain neurons there are molecularly separate requirements for Dact1 in dendrite arborization/spine formation vs. synaptogenesis. Here, we show that the developmental requirement for Dact1 during dendrite arborization, which we previously demonstrated only in hippocampal pyramidal neurons, is also present in cortical interneurons, and we discuss mechanistic implications of this finding.
authors.affiliation: Biomedical Sciences Graduate Program; University of California San Francisco; San Francisco, CA USA.
authors.forename: Annie
authors.initials: A
authors.lastname: Arguello
authors.affiliation: Biomedical Sciences Graduate Program; University of California San Francisco; San Francisco, CA USA ; Department of Psychiatry; The Nina Ireland Laboratory of Developmental Neurobiology; University of California San Francisco; San Francisco, CA USA.
authors.forename: Benjamin Nr
authors.initials: BN
authors.lastname: Cheyette
keywords: Dact1; Rho GTPase; Sholl analysis; Wnt; dendrite; interneuron; planar cell polarity