Math5 defines the ganglion cell competence state in a subpopulation of retinal progenitor cells exiting the cell cycle.
Math5 defines the ganglion cell competence state in a subpopulation of retinal progenitor cells exiting the cell cycle.
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DOI：
10.1016/j.ydbio.2012.03.006
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发表时间：
2012-05-15
影响因子：
2.7
通讯作者：
Glaser T
中科院分区：
文献类型：
--
作者：
Brzezinski JA 4th;Prasov L;Glaser T
碱性螺旋-环-螺旋（bHLH）转录因子Math 5（Atoh 7）在早期视网膜组织发生期间瞬时表达，并且是视网膜神经节细胞（RGC）发育所必需的。使用核苷脉冲追踪实验和克隆分析，我们确定祖细胞在终末分裂期间或之后激活Math 5，随着组织发生的进行，逐渐晚些时候发作。我们已经使用在严格的调控下表达Cre重组酶的小鼠BAC转基因追踪了Math 5+细胞的谱系。定量分析表明，Math 5+祖细胞表达同等水平的Math 5，并有助于成人视网膜中的每一种主要细胞类型，但严重偏向早期命运。Math 5>Cre转基因标记成人视网膜中3%的细胞，包括55%的RGC。只有11%的Math 5+祖细胞发育成RGCs;大多数成为光感受器。从视锥细胞和视杆细胞出生的比例推断，Math 5队列的命运偏差随时间变化，与剩余的神经源性人群平行。使用Math 5突变小鼠获得了类似的结果，除了神经节细胞基本上不存在，并且在谱系内晚期命运过多。我们在最早出生（胚胎第11天）的视网膜队列中鉴定了Math 5独立的RGC前体，但这些前体需要Math 5表达细胞进行分化。因此，Math 5允许在祖细胞的子集内建立RGC能力，但不足以用于命运特化。它不会自动促进或抑制非RGC命运的决定。这些数据与视网膜神经发生的渐进和时间限制模型一致，其中环境因素影响最终的组织型选择。
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.
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DOI：
10.1098/rspb.1985.0021
发表时间：
1985-01-01
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DRAGER, UC
通讯作者：
DRAGER, UC
影响因子：
5.3
作者：
Dyer, MA;Cepko, CL
通讯作者：
Cepko, CL
影响因子：
16.2
作者：
Das, T;Payer, B;Harris, WA
通讯作者：
Harris, WA
影响因子：
64.8
作者：
Erkman, L;McEvilly, RJ;Rosenfeld, MG
通讯作者：
Rosenfeld, MG
影响因子：
4.4
作者：
Brzezinski, JA;Brown, NL;Glaser, T
通讯作者：
Glaser, T