de Melo Jimmy, Du Guoyan, Fonseca Mario, Gillespie Leigh-Anne, Turk William J, Rubenstein John L R, Eisenstat David D
Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, R3E 3J7, Canada.
Development. 2005 Jan;132(2):311-22. doi: 10.1242/dev.01560. Epub 2004 Dec 16.
Dlx homeobox genes, the vertebrate homologs of Distal-less, play important roles in the development of the vertebrate forebrain, craniofacial structures and limbs. Members of the Dlx gene family are also expressed in retinal ganglion cells (RGC), amacrine and horizontal cells of the developing and postnatal retina. Expression begins at embryonic day 12.5 and is maintained until late embryogenesis for Dlx1, while Dlx2 expression extends to adulthood. We have assessed the retinal phenotype of the Dlx1/Dlx2 double knockout mouse, which dies at birth. The Dlx1/2 null retina displays a reduced ganglion cell layer (GCL), with loss of differentiated RGCs due to increased apoptosis, and corresponding thinning of the optic nerve. Ectopic expression of Crx, the cone and rod photoreceptor homeobox gene, in the GCL and neuroblastic layers of the mutants may signify altered cell fate of uncommitted RGC progenitors. However, amacrine and horizontal cell differentiation is relatively unaffected in the Dlx1/2 null retina. Herein, we propose a model whereby early-born RGCs are Dlx1 and Dlx2 independent, but Dlx function is necessary for terminal differentiation of late-born RGC progenitors.
Dlx同源框基因是Distal-less在脊椎动物中的同源物，在脊椎动物前脑、颅面结构和肢体的发育中发挥重要作用。Dlx基因家族的成员也在视网膜神经节细胞（RGC）、发育中和出生后视网膜的无长突细胞和水平细胞中表达。Dlx1的表达在胚胎第12.5天开始，并维持到胚胎发育后期，而Dlx2的表达则持续到成年期。我们评估了出生时死亡的Dlx1/Dlx2双敲除小鼠的视网膜表型。Dlx1/2基因敲除的视网膜显示神经节细胞层（GCL）减少，由于凋亡增加，分化的RGCs丢失，并且视神经相应变薄。突变体的GCL和神经母细胞层中视锥和视杆光感受器同源框基因Crx的异位表达可能意味着未分化的RGC祖细胞的细胞命运发生改变。然而，在Dlx1/2基因敲除的视网膜中，无长突细胞和水平细胞的分化相对未受影响。在此，我们提出一个模型，即早期产生的RGCs不依赖Dlx1和Dlx2，但Dlx功能对于晚期产生的RGC祖细胞的终末分化是必需的。
