Insulinoma-associated 1a (Insm1a) is required for photoreceptor differentiation in the zebrafish retina.
Insulinoma-associated 1a (Insm1a) is required for photoreceptor differentiation in the zebrafish retina.
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DOI：
10.1016/j.ydbio.2013.05.021
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发表时间：
2013-08-15
影响因子：
2.7
通讯作者：
Morris AC
中科院分区：
文献类型：
--
作者：
Forbes-Osborne MA;Wilson SG;Morris AC
锌指转录因子胰岛素瘤相关1(Insm1，以前的IA-1)在发育中的神经和神经内分泌系统中表达，是细胞类型特异性分化所必需的。虽然Insm1存在于成体大脑和斑马鱼视网膜的神经源性区域，但在成体中大部分没有表达。虽然在许多脊椎动物的胚胎视网膜中也观察到了Insm1的表达，但它在视网膜发育中的作用尚不清楚。在这里，我们证明在发育中的斑马鱼视网膜中，insm1a是光感受器分化所必需的。Insm1a缺失的胚胎为小眼球，在视杆和视锥感光细胞分化中表现出缺陷。视杆细胞对insm1a表达的缺失比视锥细胞更敏感。此外，我们提供的证据表明，insm1a调节视网膜母细胞的细胞周期进程，并在bHLH转录因子ath5/atoh7和Neurd以及光感受器规范基因crx和nr2e3的上游发挥作用。最后，我们证明了insm1a受Notch-Delta信号的负调控。综上所述，我们的数据表明，在视网膜发育过程中，Insm1影响神经元亚型分化。
The zinc-finger transcription factor Insulinoma-associated 1 (Insm1, previously IA-1) is expressed in the developing nervous and neuroendocrine systems, and is required for cell type specific differentiation. Expression of Insm1 is largely absent in the adult, although it is present in neurogenic regions of the adult brain and zebrafish retina. While expression of Insm1 has also been observed in the embryonic retina of numerous vertebrate species, its function during retinal development has remained unexplored. Here, we demonstrate that in the developing zebrafish retina, insm1a is required for photoreceptor differentiation. Insm1a-deficient embryos were microphthalmic and displayed defects in rod and cone photoreceptor differentiation. Rod photoreceptor cells were more sensitive to loss of insm1a expression than were cone photoreceptor cells. Additionally, we provide evidence that insm1a regulates cell cycle progression of retinoblasts, and functions upstream of the bHLH transcription factors ath5/atoh7 and neurod, and the photoreceptor specification genes crx and nr2e3. Finally, we show that insm1a is negatively regulated by Notch-Delta signaling. Taken together, our data demonstrate that Insm1 influences neuronal subtype differentiation during retinal development.
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