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- Title
Asymmetric Inhibition of Ulk2 Causes Left-Right Differences in Habenular Neuropil Formation.
- Authors
Taylor, Robert W.; Qi, Jenny Y.; Talaga, Anna K.; Ma, Taylur P.; Luyuan Pan; Bartholomew, Clinton R.; Klionsky, Daniel J.; Moens, Cecilia B.; Gamse, Joshua T.
- 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.
- Subjects
ZEBRA danio; BRAIN function localization; PROTEINS; NEUROPILINS; CEREBRAL dominance; CELL nuclei
- Publication
Journal of Neuroscience, 2011, Vol 31, Issue 27, p9869
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0435-11.2011