Open AccessSingle-cell transcriptional logic of cell-fate specification and axon guidance in early born retinal neurons
Author(s) -
Quentin Lo Giudice,
Marion Leleu,
Gioele La Manno,
Pierre J. Fabre
Publication year - 2019
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.178103
Subject(s) - biology , axon guidance , retina , neuroscience , microbiology and biotechnology , cell fate determination , retinal , axon , population , retinal ganglion cell , transcription factor , gene , genetics , biochemistry , demography , sociology
Retinal ganglion cells (RGC), cone photoreceptors (cones), horizontal cells (HC) and amacrine cells (AC) 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 6,067 single retinal cells to provide a comprehensive transcriptomic atlas showing the diversity of the early developing mouse retina. RNA velocities unveiled 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 amount of guidance cues for young peripheral RGC axons that express the matching receptors. Spatial transcriptionally-deduced features in sub-populations 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.