Abstract
Retinal neurogenesis occurs through partially overlapping temporal windows, driven by concerted actions of transcription factors which, in turn, may contribute to the establishment of divergent genetic programs in the developing retina by coordinating variations in chromatin landscapes. Here we comprehensively profile murine retinal progenitors by integrating next generation sequencing methods and interrogate changes in chromatin accessibility at embryonic and post-natal stages. An unbiased search for motifs in open chromatin regions identifies putative factors involved in the developmental progression of the epigenome in retinal progenitor cells. Among these factors, the transcription factor LHX2 exhibits a developmentally regulated cis-regulatory repertoire and stage-dependent motif instances. Using loss-of-function assays, we determine LHX2 coordinates variations in chromatin accessibility, by competition for nucleosome occupancy and secondary regulation of candidate pioneer factors.
Highlights
Retinal neurogenesis occurs through partially overlapping temporal windows, driven by concerted actions of transcription factors which, in turn, may contribute to the establishment of divergent genetic programs in the developing retina by coordinating variations in chromatin landscapes
Retinal neurogenesis occurs through partially overlapping temporal windows giving rise to individual cell types, as result of temporal patterning[1,2] and context-dependent regulatory functions governed by transcription factors (TFs)[3,4,5,6]
By post natal day P7, LHX2 expression becomes restricted to differentiating Müller glia and is preserved in adult Müller glia, a subset of bipolar and starburst amacrine cells[9]
Summary
Retinal neurogenesis occurs through partially overlapping temporal windows, driven by concerted actions of transcription factors which, in turn, may contribute to the establishment of divergent genetic programs in the developing retina by coordinating variations in chromatin landscapes. An unbiased search for motifs in open chromatin regions identifies putative factors involved in the developmental progression of the epigenome in retinal progenitor cells. Among these factors, the transcription factor LHX2 exhibits a developmentally regulated cis-regulatory repertoire and stage-dependent motif instances. Retinal neurogenesis occurs through partially overlapping temporal windows giving rise to individual cell types, as result of temporal patterning[1,2] and context-dependent regulatory functions governed by transcription factors (TFs)[3,4,5,6]. Embryonic deletion of Lhx[2] results in proliferative defects of glial committed precursors while early post natal ablation, as well as overexpression[9] results in the loss of glial markers and dysmorphic apical structures
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
