The role of Cxcl12b in habenular axon pathfinding in zebrafish

Abstract

The habenula is a complex region of the forebrain with multiple populations of neurons making different neurotransmitters such as dopamine, serotonin, GABA, norepinephrine, and acetylcholine. The habenula is involved in behavioral response to pain, stress, sleep, anxiety and reward.​ The habenula provides the fundamental mechanism in both survival and decision making.  Axons of the habenula project to the interpeduncular nucleus (IPN) of the midbrain. Chemokine signaling has been shown to help axons reach this target. Chemokine receptor Cxcr4b is made in the habenula, while ligand Cxcl12b is produced anterior and posterior to the developing habenula. Based on this expression pattern, we hypothesize that Cxcl12b is working as a repellant and therefore, without Cxcl12b the habenular axons will project incorrectly in the anterior/posterior direction. We have identified cxcl12b mutants carrying a transgenic line that labels the habenula and its axons with GFP. However, we have not identified any males carrying the cxcl12b mutation and the transgenic line. Due to this, we will be using the gene editing technology CRISPR to cause mutation in the cxcl12b gene injust one generation. This mutation will permit us to explore the role of Cxcl12b on habenular axon pathfinding.