Hyperactivity and Differential Gene Expression in lbx1a(−/−) Zebrafish Larvae

Lbx1 plays important roles in different processes, including the development of sensory pathways, neuronal cell fate regulation, and muscle cell precursor migration. Genetic variation in the <i>LBX1</i> locus has been associated with several human disease conditions, such as idiopathic scoliosis, congenital limb malformation, and neuropsychiatric illness, including attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders. Zebrafish (<i>Danio rerio</i>) were used to investigate the behavioral consequences of the loss of function of the two orthologs to the human <i>LBX1</i> gene, zebrafish <i>lbx1a</i> and <i>lbx1b</i>. We observed a consistent locomotor hyperactivity phenotype induced by a novel environment in <i>lbx1a</i> mutants. Repeated dark stimuli provoked similar responses in both mutant lines, including the novelty-induced hyperactivity. We performed RNAseq on total RNA isolated from the head region of mutant and wildtype larvae. Several differentially expressed genes were identified, giving more insights into Lbx1 target genes and pathways, which could be relevant regarding the evaluation of zebrafish <i>lbx1a</i> or <i>lbx1b</i> as a human disease model. Furthermore, the analysis was complemented with a comparison to the expression profile of human LBX1 overexpression in cell culture, revealing a convergence on just two commonly regulated genes, namely alpha-Internexin (<i>INA</i>) and Fibrillin-3 (<i>FBN3</i>). In conclusion, our findings might further elucidate the multitude of functions of Lbx1 and its involvement in various human disease conditions.