Kctd12 Proteins Regulate Ulk2 to Control the Development of Asymmetric Habenular Neuropil

Abstract

BIOLOGICAL SCIENCES

KCTD12 PROTEINS REGULATE ULK2 TO CONTROL THE DEVELOPMENT OF ASYMMETRIC HABENULAR NEUROPIL

ROBERT W. TAYLOR

Dissertation under the direction of Professor Joshua T. Gamse The habenular nuclei (Hb) are part of an ancient conduction pathway that controls diverse behaviors. In zebrafish, the Hb develop robust asymmetries including connectivity, morphology, and gene expression patterns. One striking example of asymmetric gene expression is the predominantly left-sided expression of kctd12.1 and the right-sided kctd12.2. Though used extensively as markers for Hb sidedness, there is a paucity of information relating to the function of Kctd12 proteins during zebrafish Hb development. We have used a cross-species yeast 2-hybrid approach to identify Unc-51-like Kinase 2 (Ulk2) as a novel Kctd12.1 interactor. We then asses the consequences of genetic manipulation of both Ulk2 and Kctd12 proteins on Hb development. We have discovered a system by which Ulk2 activity promotes the elaboration of Hb neuropil, and this activity is negatively regulated by Kctd12 proteins, leading to proper neuropil development, and perhaps shaping the asymmetric morphology of the zebrafish Hb.