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BACKGROUND

RERE is a highly conserved transcriptional co-regulator that is associated with a human neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH, OMIM: 616975).

RESULTS

We show that the zebrafish rerea mutant (babyface) robustly recapitulates optic fissure closure defects resulting from loss of RERE function, as observed in humans. These defects result from expansion of proximal retinal optic stalk (OS) and reduced expression of some of the ventral retinal fate genes due to deregulated protein signaling. Using zebrafish and cell-based assays, we determined that NEDBEH-associated human RERE variants function as hypomorphs in their ability to repress shh signaling and some exhibit abnormal nuclear localization. Inhibiting shh signaling by the protein inhibitor HPI-1 rescues coloboma, confirming our observation that coloboma in rerea mutants is indeed due to deregulation of shh signaling.

CONCLUSIONS

Zebrafish rerea mutants exhibit OS and optic fissure closure defects. The optic fissure closure defect was rescued by an shh signaling inhibitor, suggesting that this defect could arise due to deregulated shh signaling.

BACKGROUND

RERE is a highly conserved transcriptional co-regulator that is associated with a human neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH, OMIM: 616975).

RESULTS

CONCLUSIONS

背景

RERE 是一种高度保守的转录共调节因子，与伴有或不伴有脑、眼或心脏异常的人类神经发育障碍有关（NEDBEH，OMIM：616975）。

结果

我们表明，斑马鱼 rerea 突变体（babyface）强烈再现了由于 RERE 功能丧失而导致的视神经裂闭合缺陷，如在人类中观察到的那样。这些缺陷是由于近端视网膜视神经茎（OS）扩张和一些腹侧视网膜命运基因表达减少引起的，这是由于蛋白质信号失调所致。通过使用斑马鱼和基于细胞的测定法，我们确定了与 NEDBEH 相关的人类 RERE 变体在抑制 shh 信号的能力方面表现为功能低下，并且一些变体表现出异常的核定位。通过蛋白质抑制剂 HPI-1 抑制 shh 信号可挽救眼眶裂，证实了我们的观察结果，即 rerea 突变体中的眼眶裂确实是由于 shh 信号失调引起的。