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Fibroblast growth factor receptor 1 signaling transcriptionally regulates the axon guidance cue slit1

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Abstract

Axons sense molecular cues in their environment to arrive at their post-synaptic targets. While many of the molecular cues have been identified, the mechanisms that regulate their spatiotemporal expression remain elusive. We examined here the transcriptional regulation of the guidance gene slit1 both in vitro and in vivo by specific fibroblast growth factor receptors (Fgfrs). We identified an Fgf-responsive 2.3 kb slit1 promoter sequence that recapitulates spatiotemporal endogenous expression in the neural tube and eye of Xenopus embryos. We found that signaling through Fgfr1 is the main regulator of slit1 expression both in vitro in A6 kidney epithelial cells, and in the Xenopus forebrain, even when other Fgfr subtypes are present in cells. These data argue that a specific signaling pathway downstream of Fgfr1 controls in a cell-autonomous manner slit1 forebrain expression and are novel in identifying a specific growth factor receptor for in vivo control of the expression of a key embryonic axon guidance cue.

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Acknowledgements

This research was funded by an operating grant from the Canadian Institutes of Health Research (CIHR), bridge funding from Alberta Innovates-Health Solutions (AI-HS), salary awards from the CIHR Training Program in Genetic Determinants of Maternal and Child Health to JLJY, and from AI-HS to SM. We extend our thanks to M. Servetnick for fgfr2–4 probes and dominant negative constructs. We appreciate the feedback on the data from Drs. Schuurmans and Nguyen and guidance in qPCR from Dr. Visser.

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  1. Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr., NW, Calgary, AB, T2N 4N1, Canada

    Jung-Lynn Jonathan Yang, Gabriel E. Bertolesi, Carrie L. Hehr, Jillian Johnston & Sarah McFarlane

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  1. Jung-Lynn Jonathan Yang
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  2. Gabriel E. Bertolesi
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Correspondence to Sarah McFarlane.

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Yang, JL.J., Bertolesi, G.E., Hehr, C.L. et al. Fibroblast growth factor receptor 1 signaling transcriptionally regulates the axon guidance cue slit1. Cell. Mol. Life Sci. 75, 3649–3661 (2018). https://doi.org/10.1007/s00018-018-2824-x

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