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Sonic hedgehog-dependent recruitment of GABAergic interneurons into the developing visual thalamus

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dc.contributor.authorSomaiya, Rachana Devenen
dc.contributor.authorStebbins, Katelynen
dc.contributor.authorGingrich, Ellen C.en
dc.contributor.authorXie, Hehuangen
dc.contributor.authorCampbell, John N.en
dc.contributor.authorGarcia, A. Denise R.en
dc.contributor.authorFox, Michael A.en
dc.date.accessioned2023-04-24T13:24:22Zen
dc.date.available2023-04-24T13:24:22Zen
dc.date.issued2022-11en
dc.description.abstractAxons of retinal ganglion cells (RGCs) play critical roles in the development of inhibitory circuits in visual thalamus. We previously reported that RGC axons signal astrocytes to induce the expression of fibroblast growth factor 15 (FGF15), a motogen required for GABAergic interneuron migration into visual thalamus. However, how retinal axons induce thalamic astrocytes to generate Fgf15 and influence interneuron migration remains unknown. Here, we demonstrate that impairing RGC activity had little impact on interneuron recruitment into mouse visual thalamus. Instead, our data show that retinal-derived sonic hedgehog (SHH) is essential for interneuron recruitment. Specifically, we show that thalamus-projecting RGCs express SHH and thalamic astrocytes generate downstream components of SHH signaling. Deletion of RGC-derived SHH leads to a significant decrease in Fgf15 expression, as well as in the percentage of interneurons recruited into visual thalamus. Overall, our findings identify a morphogen-dependent neuron-astrocyte signaling mechanism essential for the migration of thalamic interneurons.en
dc.description.notesThis work was supported by National Institutes of Health grants EY021222 (MAF), EY030568 (MAF), EY033528 (MAF and JNC), HL153916 (JNC), and American Diabetes Association Pathway to Stop Diabetes Award 1- 18-INI-14 (JNC). We are grateful to the members of the MAF lab for scientific discussion and comments on the manuscript. We thank Dr. Stefanie Robel for providing Aldh1l1-EGFP mice, Dr. Steven W Wang for providing Atoh7-/- mice, and Dr. Anton Maximov for providing Rosa26floxstop-TeNT mice. The authors also thank Dr. Karthik Shekhar (University of California, Berkeley) for input on bioinformatics approaches.en
dc.description.sponsorshipNational Institutes of Health [EY021222, EY030568, EY033528, HL153916]; American Diabetes Association Pathway to Stop Diabetes Award [1-18-INI-14]en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.7554/eLife.79833en
dc.identifier.othere79833en
dc.identifier.pmid36342840en
dc.identifier.urihttp://hdl.handle.net/10919/114757en
dc.identifier.volume11en
dc.language.isoenen
dc.publisherElife Sciencesen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectthalamusen
dc.subjectinterneuronen
dc.subjectretinal ganglion cellen
dc.subjectsonic hedgehogen
dc.subjectastrocytesen
dc.subjectactivityen
dc.subjectMouseen
dc.titleSonic hedgehog-dependent recruitment of GABAergic interneurons into the developing visual thalamusen
dc.title.serialeLifeen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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