Acknowledgements: This work is supported by NSF IOS-2048080, NINDS R01 NS123439 01, and a UChicago Faculty Diversity Grant to R.A.C, F31NS120458 and T32 GM007183 to M.L-.R., and NIH R01NS070644 to Richard S. Mann (for support of L.V.). This work is also supported by funds from UChicago Biological Science Division, Committee of Developmental Biology and Department of Molecular Genetics & Cellular Biology. We thank the Bloomington Drosophila Stock Center (NIH P40OD018537) for fly lines. The monoclonal antibodies 4F3 and 8B12 were developed by Goodman, C., and the 8A1-S antibody was developed by Mary Logan, and they were obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at the University of Iowa, Department of Biology. We would like to thank Claude Desplan (New York University), Richard Mann (Columbia University), Robin E. Harris (Arizona State University) and Jean-Paul Vincent (the Francis Crick Institute) for sharing resources. We would also like to thank Richard Fehon, Ellie Heckscher, David Pincus, Audrina Daisy, Viola Nawrocka and members from the Carrillo laboratory for valuable discussions and comments. Cartoons in Figs. 2f, 3i, 4i, 5a, e, 6a, e, 7a, 8a, b, 9d, and Supplementary Figs. 4a, 5a, 6g, 7g, 8g, 9g, 10h, 11h, 12a, g were created with BioRender.com (license to Robert Carrillo).

Funder: U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)