POU domain factor Brn-3b is essential for retinal ganglion cell differentiation and survival but not for initial cell fate specification
POU domain factor Brn-3b is essential for retinal ganglion cell differentiation and survival but not for initial cell fate specification
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DOI：
10.1006/dbio.1999.9280
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发表时间：
1999-06-15
影响因子：
2.7
通讯作者：
Klein, WH
中科院分区：
文献类型：
--
作者：
Gan, L;Wang, SW;Klein, WH
虽然哺乳动物的视网膜在解剖学和生理学层面已被充分了解，但对于产生视网膜高度有序模式及其多样神经元细胞类型的机制却知之甚少。先前的研究表明，POU - IV类转录因子Brn - 3b（Brn - 3.2）的基因破坏导致出生后小鼠视网膜中大多数视网膜神经节细胞缺失。在此，我们利用敲入brn - 3b基因座的lacZ和人胎盘碱性磷酸酶基因来追踪发育中的视网膜内brn - 3b突变细胞的命运。我们发现，Brn - 3b对于视网膜神经节细胞命运的初始确定以及神经节细胞向神经节细胞层的迁移并非必需。然而，Brn - 3b对于视网膜神经节细胞的正常分化至关重要；没有它，细胞会发生增强的凋亡。缺乏brn - 3b的视网膜神经节细胞在发育的适当时间伸出突起，但这些突起杂乱无章，导致视神经变薄。来自brn - 3b缺失胚胎的外植视网膜在体外培养时也会伸出突起，但这些突起比野生型视网膜中的更短且更少成束。超微结构和标记分析表明，突变神经节细胞的突起具有树突而非轴突的特征，这表明突变细胞形成树突来替代轴突。这些结果表明，Brn - 3b调节一些基因的活性，这些基因的产物在视网膜神经节细胞轴突的形成中起关键作用。（C）1999年学术出版社
While the mammalian retina is well understood at the anatomical and physiological levels, little is known about the mechanisms that give rise to the retina's highly ordered pattern or its diverse neuronal cell types. Previous investigations have shown that gene disruption of the POU-IV class transcription factor Brn-3b (Brn-3.2) resulted in the loss of most retinal ganglion cells in retinas of postnatal mice. Here, we used lacZ and human placental alkaline phosphatase genes knocked into the brn-3b locus to follow the fate of brn-3b-mutant cells in the developing retina. We found that Brn-3b was not required for the initial commitment of retinal ganglion cell fate or for the migration of ganglion cells to the ganglion cell layer. However, Brn-3b was essential for the normal differentiation of retinal ganglion cells; without it, the cells underwent enhanced apoptosis. Retinal ganglion cells lacking brn-3b extended processes at the appropriate time in development, but these processes were disorganized, resulting in a thinner optic nerve. Explanted retinas from brn-3b-null embryos also extended processes when cultured in vitro, but the processes were shorter and less bundled than in wild-type retinas. Ultrastructural and marker analyses showed that the processes of mutant ganglion cells had dendritic rather than axonal features, suggesting that mutant cells formed dendrites in place of axons. These results suggest that Brn-3b regulates the activity of genes whose products play essential roles in the formation of retinal ganglion cell axons. (C) 1999 Academic Press.