Abstract
The basic helix-loop-helix (bHLH) transcription factor . Math5 (. Atoh7) is transiently expressed during early retinal histogenesis and is necessary for retinal ganglion cell (RGC) development. Using nucleoside pulse-chase experiments and clonal analysis, we determined that progenitor cells activate . Math5 during or after the terminal division, with progressively later onset as histogenesis proceeds. We have traced the lineage of . Math5+ cells using mouse BAC transgenes that express Cre recombinase under strict regulatory control. Quantitative analysis showed that . Math5+ progenitors express equivalent levels of . Math5 and contribute to every major cell type in the adult retina, but are heavily skewed toward early fates. The Math5. >. Cre transgene labels 3% of cells in adult retina, including 55% of RGCs. Only 11% of . Math5+ progenitors develop into RGCs; the majority become photoreceptors. The fate bias of the . Math5 cohort, inferred from the ratio of cone and rod births, changes over time, in parallel with the remaining neurogenic population. Comparable results were obtained using . Math5 mutant mice, except that ganglion cells were essentially absent, and late fates were overrepresented within the lineage. We identified . Math5-independent RGC precursors in the earliest born (embryonic day 11) retinal cohort, but these precursors require . Math5-expressing cells for differentiation. . Math5 thus acts permissively to establish RGC competence within a subset of progenitors, but is not sufficient for fate specification. It does not autonomously promote or suppress the determination of non-RGC fates. These data are consistent with progressive and temporal restriction models for retinal neurogenesis, in which environmental factors influence the final histotypic choice.
Original language | English (US) |
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Pages (from-to) | 395-413 |
Number of pages | 19 |
Journal | Developmental Biology |
Volume | 365 |
Issue number | 2 |
DOIs | |
State | Published - May 15 2012 |
Keywords
- Atonal
- BAC transgenic
- BHLH
- Cell fate determination
- Cre recombinase
- Expression fate mapping
- Genetics
- Lineage
- Mouse
- Optic nerve
- Retina
ASJC Scopus subject areas
- Developmental Biology
- Cell Biology
- Molecular Biology