Dlx1, Dlx2, Pax6, Brn3b, and Chx10 homeobox gene expression defines the retinal ganglion and inner nuclear layers of the developing and adult mouse retina

Dlx1, Dlx2, Pax6, Brn3b, and Chx10 homeobox gene expression defines the retinal ganglion and inner nuclear layers of the developing and adult mouse retina
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DOI:
10.1002/cne.10674
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发表时间:
2003-06-23
影响因子:
2.5
通讯作者:
Eisenstat, DD
Eisenstat, DD
中科院分区:
医学3区
文献类型:
--
作者:
de Melo, J;Qiu, XG;Eisenstat, DD

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非远端同源盒基因在发育中的前脑中表达。我们评估了Dlx基因在发育和成年小鼠视网膜中的表达。Dlx 1和Dlx 2在胚胎第12.5天(E)在视网膜神经祖细胞中检测到(Eisenstat等人[1999] J.Comp.Neurol. 217-237)。在E13.5,四种同源结构域蛋白DLX、BRN 3b、PAX 6和CHX 10的表达在视网膜神经上皮中定义了不同但重叠的结构域。到出生后第0天(P),DLX 2在成神经细胞层和由神经节和移位的无长突细胞组成的神经节细胞层(GCL)中表达。DLX 1表达类似于DIM至P0,但在出生后降低。在成人中,DLX 2定位于神经节、无长突和水平细胞,如通过与视网膜细胞特异性标志物的共表达所确定的。DLX 2与γ-氨基丁酸(GABA)、谷氨酸脱羧酶(GAD)65和GAD 67在内核层(INL)和GCL中的表达一致。在成人中,DLX 2与BRN 3b在神经节细胞中共表达; PAX 6在无长突细胞、水平细胞和神经节细胞中共表达; Chx 10在一些双极细胞中共表达。我们预测,这些同源异型盒基因和其他基因的组合代码指定视网膜细胞的命运。我们的研究结果支持Dlx 1和Dlx 2在视网膜发育和终末分化和/或维持成人INL中间神经元和神经节细胞中的可能作用。DLX 2与小鼠视网膜中GABA表达的相关性密切反映了DLX 2与胚胎前脑(包括新皮层、嗅球和海马)中GABA能神经元分化的关系,表明Dlx基因在发育中的中枢神经系统中的功能保守。
Distal-less homeobox genes are expressed in the developing forebrain. We assessed Dlx gene expression in the developing and adult mouse retina. Dlx1 and Dlx2 are detected in retinal neuroprogenitors by embryonic day (E) 12.5 (Eisenstat et al. [1999] J. Comp. Neurol. 217-237). At E13.5, the expression of four homeodomain proteins, DLX, BRN3b, PAX6, and CHX10, define distinct yet overlapping domains in the retinal neuroepithelium. By postnatal day (P) 0, DLX2 is expressed in the neuroblastic layer and the ganglion cell layer (GCL) consisting of ganglion and displaced amacrine cells. DLX1 expression resembles DIM to P0 but decreases postnatally. In the adult, DLX2 is localized to ganglion, amacrine, and horizontal cells as determined by coexpression with retinal cell-specific markers. There is coincident expression of DLX2 with gamma-aminobutyric acid (GABA), glutamic acid decarboxylase (GAD)65, and GAD67 in the inner nuclear layer (INL) and GCL. In the adult, DLX2 is coexpressed with BRN3b in ganglion cells; PAX6 in amacrine, horizontal, and ganglion cells; and Chx10 in some bipolar cells. We predict that a combinatorial code of these homeobox genes and others specify retinal cell fate. Our results support a possible role for Dlx1 and Dlx2 in inner retinal development and in the terminal differentiation and/or maintenance of INL interneurons and ganglion cells in the adult. The correlation of DLX2 with GABA expression in the mouse retina closely mirrors the relationship of DLX2 to GABAergic neuronal differentiation in the embryonic forebrain, including neocortex, olfactory bulb and hippocampus, signifying a conservation of function of Dlx genes in the developing central nervous system.