Kctd12 and Ulk2 Partner to Regulate Dendritogenesis and Behavior in the Habenular Nuclei

• Published in: PloS one Vol. 9; no. 10; p. e110280
• Main Authors: Lee, Stacey, Page-McCaw, Patrick, Gamse, Joshua T.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.10.2014; Public Library of Science (PLoS)
• Subjects: Amino acids; Animals; Anxiety; Anxiety - metabolism; Anxiety - pathology; Behavior; Behavior, Animal; Biology and Life Sciences; Brain research; Cation Transport Proteins - metabolism; Dendrites; Dendrites - metabolism; Developmental biology; Embryos; Environment; Environmental effects; Feedback; Gene expression; Gene Knockdown Techniques; Genetic engineering; Habenula - cytology; Habenula - growth & development; Kinases; Limbic system; Mental depression; Morphogenesis; Nerve Tissue Proteins - metabolism; Neurons; Nuclei; Patients; Proline; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases; Proteins; Schizophrenia; Serine; Stimuli; Telencephalon; Zebrafish; Zebrafish - growth & development; Zebrafish - metabolism; Zebrafish Proteins - chemistry; Zebrafish Proteins - deficiency; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; United States > US; Tennessee; Nashville Tennessee
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0110280

The habenular nuclei of the limbic system regulate responses, such as anxiety, to aversive stimuli in the environment. The habenulae receive inputs from the telencephalon via elaborate dendrites that form in the center of the nuclei. The kinase Ulk2 positively regulates dendritogenesis on habenular neurons, and in turn is negatively regulated by the cytoplasmic protein Kctd12. Given that the habenulae are a nexus in the aversive response circuit, we suspected that incomplete habenular dendritogenesis would have profound implications for behavior. We find that Ulk2, which interacts with Kctd12 proteins via a small proline-serine rich domain, promotes branching and elaboration of dendrites. Loss of Kctd12 results in increased branching/elaboration and decreased anxiety. We conclude that fine-tuning of habenular dendritogenesis during development is essential for appropriate behavioral responses to negative stimuli.