The vertebrate eye anlage grows out of the brain and folds into bilayered optic cups. The eye is patterned along multiple axes, precisely controlled by genetic programs, to delineate neural retina, pigment epithelium, and optic stalk tissues. Pax genes encode developmental regulators of key morphogenetic events, with Pax2 being essential for interpreting inductive signals, including in the eye. PAX2 mutations cause ocular coloboma, when the ventral optic fissure fails to close. Previous studies established that Pax2 is necessary for fissure closure and to maintain the neural retina -- glial optic stalk boundary. Using a Pax2^GFP/+ knock-in allele we discovered that the mutant optic nerve head (ONH) lacks molecular boundaries with the retina and RPE, rendering the ONH larger than normal. This was preceded by ventronasal cup mispatterning, a burst of overproliferation and followed by optic cup apoptosis. Our findings support the hypothesis that ONH cells are tripotential, requiring Pax2 to remain committed to glial fates. This work extends current models of ocular development, contributes to broader understanding of tissue boundary formation and informs the underlying mechanisms of human coloboma.

脊椎动物的眼原基从大脑中长出并折叠成双层视杯。眼睛沿多个轴图案化，由基因程序精确控制，以描绘神经视网膜、色素上皮和视柄组织。Pax 基因编码关键形态发生事件的发育调节因子，Pax2对于解释感应信号至关重要，包括在眼睛中。当腹侧视裂未能闭合时，PAX2突变会导致眼部缺损。先前的研究表明，Pax2是裂隙闭合和维持神经视网膜——神经胶质视柄边界所必需的。使用Pax2 ^GFP/+敲入等位基因我们发现突变的视神经乳头（ONH）缺乏与视网膜和RPE的分子边界，使得ONH比正常大。在此之前是腹鼻杯模式错误，过度增殖爆发，随后是视杯细胞凋亡。我们的研究结果支持 ONH 细胞是三电位的假设，需要Pax2继续致力于神经胶质的命运。这项工作扩展了当前的眼部发育模型，有助于更广泛地了解组织边界的形成，并为人类缺损的潜在机制提供信息。