title: Regional effects of endocannabinoid, BDNF and FGF receptor signalling on neuroblast motility and guidance along the rostral migratory stream.
abstract: During development and after birth neural stem cells in the subventricular zone (SVZ) generate neuroblasts that migrate along the rostral migratory stream (RMS) to populate the olfactory bulb (OB) with neurons. Multiple factors promote neuroblast migration, but the contribution that many of these make to guidance within the intact RMS is not known. In the present study we have characterised in detail how endocannabinoid (eCB), BDNF and FGF receptor (FGFR) signalling regulates motility and guidance, and also determined whether any of these receptors operate in a regionally restricted manner. We used in vivo electroporation in postnatal mice to fluorescently label neuroblasts, and live cell imaging to detail their migratory properties. Cannabinoid receptor antagonists rendered neuroblasts less mobile, and when they did move guidance was lost. Similar results were obtained when eCB synthesis was blocked with diacylglycerol lipase (DAGL) inhibitors, and importantly eCB function is required for directed migration at both ends of the RMS. Likewise, inhibition of BDNF signalling disrupted motility and guidance in a similar manner along the entire RMS. In contrast, altering FGFR signalling inhibits motility and perturbs guidance, but only at the beginning of the stream. Inhibition of FGFR signalling in vivo also reduces the length of the leading process on migratory neuroblasts in a graded manner along the RMS. These results provide evidence for a guidance function for all three of the above receptor systems in the intact RMS, but show that FGFR signalling is unique as it is required in a regionally specific manner.
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, United Kingdom.
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, United Kingdom.
authors.forename: Madeleine J
authors.initials: MJ
authors.lastname: Oudin
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, United Kingdom.
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Gajendra
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, United Kingdom.
authors.forename: Martina
authors.initials: M
authors.lastname: Sonego
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, United Kingdom.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Falenta
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, United Kingdom.
authors.forename: Gareth
authors.initials: G
authors.lastname: Williams
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, United Kingdom. Electronic address: giovanna.lalli@kcl.ac.uk.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lalli
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, United Kingdom. Electronic address: patrick.doherty@kcl.ac.uk.
authors.forename: Patrick
authors.initials: P
authors.lastname: Doherty
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002465:Cell Movement; D005260:Female; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D055495:Neurogenesis; D009830:Olfactory Bulb / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism*; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D063387:Cannabinoid Receptor Antagonists; D043882:Receptors, Cannabinoid; D017468:Receptors, Fibroblast Growth Factor; D020813:Receptor, trkB; D008071:Lipoprotein Lipase
keywords: BDNF; Endocannabinoid; FGF; Neuroblast migration rostral migratory stream