PgmNr Z6162: Characterization of DPP6 Neuronal Expression in Zebrafish (Danio rerio).

Authors:
E. P. Kite 1 ; L. Burghi 2 ; K. Hu 2 ; M. Geng 2 ; B. R. Bill 1


Institutes
1) University of Texas at Tyler, Tyler, TX; 2) University of California Los Angeles, Los Angeles, CA.


Abstract:

Autism spectrum disorders (ASDs) are a heterogeneous set of developmental disorders with complex etiology. Dipeptidyl-Pepitdase 6 (DPP6) is a proposed autism candidate gene. Mouse models have been informative for function of this potassium channel regulator; however, a zebrafish model could provide a vehicle for high-throughput pharmaceutical screens or gene-gene interaction studies. Therefore, our goal was to determine the suitability of the zebrafish homologs for these studies. In zebrafish, there exists two homologs of DPP6, dpp6a (63.4% identity to DPP6) and dpp6b (59% identity to DPP6). Utilizing qRT-PCR and in situ hybridization, we identified expression of dpp6b as early as 2 days post fertilization (dpf) continuing through adult. Specifically, we observed staining within the zebrafish thalamus, hypothalamus, periventricular Gray of the optic tectum, and torus longitudinalis utilizing in situ hybridization for dpp6b expression. A more extensive analysis was performed with immunohistochemistry utilizing a commercial antibody raised against the human DPP6 synthetic peptide, expression was observed in brain areas similar to that of the in situ; however, we saw broader staining in the cerebellum, fasciculus retroflexus, and several sensory-associated neurons. Based on conservation, expression, and the ability of the human antibody to cross react with the zebrafish dpp6, we propose that the zebrafish homologs will be functionally similar; therefore, a good tool for future studies.  Preliminary studies with morpholino oligonucleotides and TALEN knockouts are being developed to determine anatomical and behavioral neuronal phenotypes.



ZFIN Genetics Index
1. dpp6a
2. dpp6b