The lateral line is a mechanosensory system used by fish to sense the movement of water. It is evolutionarily related to the inner-ear in humans. For both organisms, the binding of the CXCL12 (SDF-1 ligand) to the CXCR4 receptor induces conformational changes needed to activate signal transduction. This signaling results in numerous cellular responses such as cell fate, chemotaxis, and gene transcription. Interestingly, researchers have found that another signaling molecule, CXCL14, can also bind to the CXCR4 receptor with high affinity (Tanegashima et al., 2013). As a result, we hypothesize that CXCL14 modulates CXCL12-mediated chemotaxis, presumably acting as an allosteric regulator.
We are concerned with the allosteric relationship between CXCL14 and CXCL12 and how those relationships affect gene expression in lateral line development. In order to study this interaction, zebrafish were used as our model organism. To examine the effects of CXCL14 on CXCL12-mediated gene transcription, zebrafish embryos were microinjected with CXCL14 antisense morpholino and incubated for a period of three timepoints: 24 dpf, 36 dpf, and 48 dpf, when lateral line development occurs. Our preliminary results suggest that the absence of CXCL14 affects the gene expression of CXCL14, CXCL12, CXCR4, CXCR7, epcam, claudin, and snail1b during lateral line development, thereby suggesting the allosteric capabilities of CXCL14. Further studies will be conducted to determine the degree to which CXCL14 affects the transcription levels of these genes.
Level of Honors
magna cum laude
Calderon-Zavala, Ariana, "Examining lateral line development through CXCL14 modulation of CXCL12-CXCR4 mediated gene expression in Danio rerio" (2019). Lawrence University Honors Projects. 144.