Timing and topography of cell genesis in the rat retina
Timing and topography of cell genesis in the rat retina
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DOI：
10.1002/cne.20134
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发表时间：
2004-06-21
影响因子：
2.5
通讯作者：
LaVail, MM
中科院分区：
文献类型：
--
作者：
Rapaport, DH;Wong, LL;LaVail, MM
为了了解脊椎动物视网膜中细胞命运决定的机制，需要建立主要细胞类型产生的时间过程。这将有助于定义和解释基因表达模式，分化波，能力的时间和范围，以及许多其他涉及命运获得的发育过程。一个彻底的视网膜细胞“出生”的研究还没有进行实验室大鼠，即使它是许多当代脊椎动物视网膜发育研究的选择物种。我们用H-3-TdR研究了细胞发生的时间和空间模式。在胚胎第8天（E）和出生后第13天（P）之间，向妊娠大鼠或大鼠幼崽单次注射H-3-TdR。出生前注射的大鼠的后代被交付，所有动物均存活至成熟。通过视网膜切片的放射自显影使标记的细胞可视化。大鼠视网膜细胞的发生开始于E10左右，大约50%的细胞在P1出生，视网膜发生在P12左右完成。在视网膜神经节细胞层中发现第一个有丝分裂后细胞，直径为9-15 μ m。这个范围包括小到中等直径的视网膜神经节细胞和大的移位的无长突细胞。通过确定每种表型的总细胞群的5%、50%和95%变为有丝分裂后的年龄来确定细胞发生的顺序。除了少数例外，细胞类型按以下顺序达到这些发育里程碑：视网膜神经节细胞、水平细胞、视锥细胞、无长突细胞、视杆细胞、双极细胞和Muller胶质细胞。对于每种类型，第一个产生的细胞位于中央视网膜，最后一个细胞位于周边视网膜。在细胞发生的序列中，可以根据细胞产生的时间、动力学和地形梯度的差异检测两个或三个阶段。我们的研究结果表明，大鼠视网膜细胞的生成顺序与灵长类视网膜相似，其中视网膜发生跨越100多天。就序列反映细胞命运决定的潜在机制而言，它们似乎是保守的。(C)2004 Wiley-Liss，Inc.
To understand the mechanisms of cell fate determination in the vertebrate retina, the time course of the generation of the major cell types needs to be established. This will help define and interpret patterns of gene expression, waves of differentiation, timing and extent of competence, and many of the other developmental processes involved in fate acquisition. A thorough retinal cell "birthdating" study has not been performed for the laboratory rat, even though it is the species of choice for many contemporary developmental studies of the vertebrate retina. We investigated the timing and spatial pattern of cell genesis using H-3-thymidine (H-3-TdR). A single injection of H-3-TdR was administered to pregnant rats or rat pups between embryonic day (E) 8 and postnatal day (P) 13. The offspring of prenatally injected rats were delivered and all animals survived to maturity. Labeled cells were visualized by autoradiography of retinal sections. Rat retinal cell genesis commenced around E10, 50% of cells were born by approximately P1, and retinogenesis was complete near P12. The first postmitotic cells were found in the retinal ;ganglion cell layer and were 9-15 mum in diameter. This range includes small to medium diameter retinal ganglion cells and large displaced amacrine cells. The sequence of cell genesis was established by determining the age at which 5, 50, and 95% of the total population of cells of each phenotype became postmitotic. With few exceptions, the cell types reached these developmental landmarks in the following order: retinal ganglion cells, horizontal cells, cones, amacrine cells, rods, bipolar cells, and Muller glia. For each type, the first cells generated were located in the central retina and the last cells in the peripheral retina. Within the sequence of cell genesis, two or three phases could be detected based on differences in timing, kinetics, and topographic gradients of cell production. Our results show that retinal cells in the rat are generated in a sequence similar to that of the primate retina, in which retinogenesis spans more than 100 days. To the extent that sequences reflect underlying mechanisms of cell fate determination, they appear to be conserved. (C) 2004 Wiley-Liss, Inc.