Retinal ganglion cells (RGCs), cone photoreceptors (cones), horizontal cells and amacrine cells are the first classes of neurons produced in the retina. However, an important question is how this diversity of cell states is transcriptionally produced. Here, we profiled 6067 single retinal cells to provide a comprehensive transcriptomic atlas showing the diversity of the early developing mouse retina. RNA velocities unveiled the dynamics of cell cycle coordination of early retinogenesis and define the transcriptional sequences at work during the hierarchical production of early cell-fate specification. We show that RGC maturation follows six waves of gene expression, with older-generated RGCs transcribing increasing amounts of guidance cues for young peripheral RGC axons that express the matching receptors. Spatial transcriptionally deduced features in subpopulations of RGCs allowed us to define novel molecular markers that are spatially restricted. Finally, the isolation of such a spatially restricted population, ipsilateral RGCs, allowed us to identify their molecular identity at the time they execute axon guidance decisions. Together, these data represent a valuable resource shedding light on transcription factor sequences and guidance cue dynamics during mouse retinal development.
Keywords: Axon guidance; Cell-fate specification; Mouse; Neurogenesis; Retinal development; Retinal ganglion cell; Single-cell RNA-seq.
© 2019. Published by The Company of Biologists Ltd.
Conflict of interest statement
Competing interestsThe authors declare no competing or financial interests.
Ephrin-B2 Elicits Differential Growth Cone Collapse and Axon Retraction in Retinal Ganglion Cells From Distinct Retinal RegionsTJ Petros et al. Dev Neurobiol 70 (11), 781-94. PMID 20629048.The circuit for binocular vision and stereopsis is established at the optic chiasm, where retinal ganglion cell (RGC) axons diverge into the ipsilateral and contralateral …
A Comprehensive Negative Regulatory Program Controlled by Brn3b to Ensure Ganglion Cell Specification From Multipotential Retinal PrecursorsF Qiu et al. J Neurosci 28 (13), 3392-403. PMID 18367606.The retinal ganglion cells (RGCs) are the sole output neurons in the retina that form the optic nerve and convey light signals detected by photoreceptors to the higher vi …
Delayed Neurogenesis Leads to Altered Specification of Ventrotemporal Retinal Ganglion Cells in Albino MiceP Bhansali et al. Neural Dev 9, 11. PMID 24885435.A delay in neurogenesis in the albino retina is linked to the alteration of RGC subtype specification and consequently leads to the reduced ipsilateral projection that ch …
Expression and Function of the LIM-homeodomain Transcription Factor Islet-1 in the Developing and Mature Vertebrate RetinaR Bejarano-Escobar et al. Exp Eye Res 138, 22-31. PMID 26122047. - ReviewThe LIM-homeodomain transcription factor Islet-1 (Isl1) has been widely used as a marker of different subtypes of neurons in the developing and mature retina of vertebrat …
Neurogenesis and Specification of Retinal Ganglion CellsKT Nguyen-Ba-Charvet et al. Int J Mol Sci 21 (2). PMID 31936811. - ReviewAcross all species, retinal ganglion cells (RGCs) are the first retinal neurons generated during development, followed by the other retinal cell types. How are retinal pr …
Cited by 1 PubMed Central articles
Retinogenesis of the Human Fetal Retina: An Apical Polarity PerspectivePMJ Quinn et al. Genes (Basel) 10 (12). PMID 31795518. - ReviewThe Crumbs complex has prominent roles in the control of apical cell polarity, in the coupling of cell density sensing to downstream cell signaling pathways, and in regul …