Zhang Samuel Shao-Min, Xu Xuming, Liu Mu-Gen, Zhao Hongyu, Soares Marcelo Bento, Barnstable Colin J, Fu Xin-Yuan
Departments of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, Connecticut, USA.
BMC Dev Biol. 2006 Oct 17;6:48. doi: 10.1186/1471-213X-6-48.
Between embryonic day 12 and postnatal day 21, six major neuronal and one glia cell type are generated from multipotential progenitors in a characteristic sequence during mouse retina development. We investigated expression patterns of retina transcripts during the major embryonic and postnatal developmental stages to provide a systematic view of normal mouse retina development,
A tissue-specific cDNA microarray was generated using a set of sequence non-redundant EST clones collected from mouse retina. Eleven stages of mouse retina, from embryonic day 12.5 (El2.5) to postnatal day 21 (PN21), were collected for RNA isolation. Non-amplified RNAs were labeled for microarray experiments and three sets of data were analyzed for significance, hierarchical relationships, and functional clustering. Six individual gene expression clusters were identified based on expression patterns of transcripts through retina development. Two developmental phases were clearly divided with postnatal day 5 (PN5) as a separate cluster. Among 4,180 transcripts that changed significantly during development, approximately 2/3 of the genes were expressed at high levels up until PN5 and then declined whereas the other 1/3 of the genes increased expression from PN5 and remained at the higher levels until at least PN21. Less than 1% of the genes observed showed a peak of expression between the two phases. Among the later increased population, only about 40% genes are correlated with rod photoreceptors, indicating that multiple cell types contributed to gene expression in this phase. Within the same functional classes, however, different gene populations were expressed in distinct developmental phases. A correlation coefficient analysis of gene expression during retina development between previous SAGE studies and this study was also carried out.
This study provides a complementary genome-wide view of common gene dynamics and a broad molecular classification of mouse retina development. Different genes in the same functional clusters are expressed in the different developmental stages, suggesting that cells might change gene expression profiles from differentiation to maturation stages. We propose that large-scale changes in gene regulation during development are necessary for the final maturation and function of the retina.
在胚胎第12天至出生后第21天之间，小鼠视网膜发育过程中，多能祖细胞按特定顺序产生六种主要神经元细胞类型和一种神经胶质细胞类型。我们研究了胚胎期和出生后主要发育阶段视网膜转录本的表达模式，以提供正常小鼠视网膜发育的系统视图。
使用从小鼠视网膜收集的一组序列无冗余的EST克隆构建了组织特异性cDNA微阵列。收集了小鼠视网膜从胚胎第12.5天（E12.5）到出生后第21天（PN21）的11个阶段用于RNA分离。未扩增的RNA被标记用于微阵列实验，并对三组数据进行了显著性、层次关系和功能聚类分析。根据转录本在视网膜发育过程中的表达模式，鉴定出六个单独的基因表达簇。以出生后第5天（PN5）为一个单独的簇，明显划分出两个发育阶段。在发育过程中显著变化的4180个转录本中，约2/3的基因在PN5之前高水平表达，然后下降，而另外1/3的基因从PN5开始表达增加，并至少在PN21时保持在较高水平。观察到的基因中不到1%在两个阶段之间表达出现峰值。在后期增加的群体中，只有约40%的基因与视杆光感受器相关，表明在此阶段多种细胞类型对基因表达有贡献。然而，在相同的功能类别中，不同的基因群体在不同的发育阶段表达。还对先前SAGE研究与本研究中视网膜发育过程中的基因表达进行了相关系数分析。
本研究提供了关于常见基因动态的全基因组互补视图以及小鼠视网膜发育的广泛分子分类。同一功能簇中的不同基因在不同发育阶段表达，表明细胞可能在从分化到成熟阶段改变基因表达谱。我们提出，发育过程中基因调控的大规模变化对于视网膜的最终成熟和功能是必要的。
