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Asymmetric inhibition of Ulk2 causes left-right differences in habenular neuropil formation.

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.

Pubmed ID: 21734278

Authors

  • Taylor RW
  • Qi JY
  • Talaga AK
  • Ma TP
  • Pan L
  • Bartholomew CR
  • Klionsky DJ
  • Moens CB
  • Gamse JT

Journal

The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

July 6, 2011

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM53396
  • Agency: NHLBI NIH HHS, Id: HC054534
  • Agency: NHGRI NIH HHS, Id: HG002995
  • Agency: NIGMS NIH HHS, Id: R01 GM053396
  • Agency: NICHD NIH HHS, Id: R01 HD054534
  • Agency: NICHD NIH HHS, Id: R01 HD054534-05
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Alkylating Agents
  • Animals
  • Animals, Genetically Modified
  • Cation Transport Proteins
  • Ethylnitrosourea
  • Functional Laterality
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins
  • Habenula
  • Immunoprecipitation
  • Inhibition (Psychology)
  • Larva
  • Mutation
  • Nerve Tissue Proteins
  • Neuropil
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Tubulin
  • Two-Hybrid System Techniques
  • Zebrafish
  • Zebrafish Proteins