title: Asymmetric inhibition of Ulk2 causes left-right differences in habenular neuropil formation.
abstract: Studies of the zebrafish epithalamus have provided recent insights into the development of left-right brain asymmetry, which is crucial to normal human brain function. The habenular nuclei of zebrafish are robustly asymmetric, with dense elaboration of neuropil only in the left lateral subnucleus. Because this feature is tightly correlated with asymmetric expression of K(+) channel tetramerization domain-containing proteins 12.1 and 12.2 (Kctd12.1/12.2), we screened for Kctd12.1-interacting proteins to identify molecular mechanisms leading to neuropil asymmetry, and uncovered a novel interaction between Kctd12.1 and Unc-51-like kinase 2 (Ulk2). We show here that knockdown of Ulk2 or overexpression of Kctd12 proteins reduces asymmetric neuropil elaboration. Conversely, overexpression of Ulk2 or mutation of kctd12 genes causes excess neuropil elaboration. We conclude that Ulk2 activity promotes neuropil elaboration while Kctd12 proteins limit Ulk2 activity asymmetrically. This work describes a regulatory mechanism for neuronal process extension that may be conserved in other developmental contexts in addition to the epithalamus.
authors: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37205, USA.
authors: Robert W
authors: RW
authors: Taylor
authors: Jenny Y
authors: JY
authors: Qi
authors: Anna K
authors: AK
authors: Talaga
authors: Taylur P
authors: TP
authors: Ma
authors: Luyuan
authors: L
authors: Pan
authors: Clinton R
authors: CR
authors: Bartholomew
authors: Daniel J
authors: DJ
authors: Klionsky
authors: Cecilia B
authors: CB
authors: Moens
authors: Joshua T
authors: JT
authors: Gamse
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D005038:Ethylnitrosourea / Q000494:pharmacology; D007839:Functional Laterality / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D019262:Habenula / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development / Q000293:injuries; D047468:Immunoprecipitation; D007266:Inhibition, Psychological; D007814:Larva; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D019581:Neuropil / Q000187:drug effects / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000477:Alkylating Agents; D027682:Cation Transport Proteins; D009419:Nerve Tissue Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014404:Tubulin; D029961:Zebrafish Proteins; C472905:kctd12.1 protein, zebrafish; D049452:Green Fluorescent Proteins; D017346:Protein Serine-Threonine Kinases; D005038:Ethylnitrosourea