Opposing interactions between homothorax and Lobe define the ventral eye margin of Drosophila eye.

Patterning in multi-cellular organisms involves progressive restriction of cell fates by generation of boundaries to divide an organ primordium into smaller fields. We have employed the Drosophila eye model to understand the genetic circuitry responsible for defining the boundary between the eye and the head cuticle on the ventral margin. The default state of the early eye is ventral and depends on the function of Lobe (L) and the Notch ligand Serrate (Ser). We identified homothorax (hth) as a strong enhancer of the L mutant phenotype of loss of ventral eye. Hth is a MEIS class gene with a highly conserved Meis-Hth (MH) domain and a homeodomain (HD). Hth is known to bind Extradenticle (Exd) via its MH domain for its nuclear translocation. Loss-of-function of hth, a negative regulator of eye, results in ectopic ventral eye enlargements. This phenotype is complementary to the L mutant phenotype of loss-of-ventral eye. However, if L and hth interact during ventral eye development remains unknown. Here we show that (i) L acts antagonistically to hth, (ii) Hth is upregulated in the L mutant background, and (iii) MH domain of Hth is required for its genetic interaction with L, while its homeodomain is not, (iv) in L mutant background ventral eye suppression function of Hth involves novel MH domain-dependent factor(s), (v) Nuclear localization of Exd is not sufficient to mediate the Hth function in the L mutant background. Further, Exd is not a critical rate-limiting factor for the Hth function. Thus, optimum levels of L and Hth are required to define the boundary between the developing eye and head cuticle on the ventral margin.

多细胞生物的模式形成涉及通过产生边界将器官原基划分为更小区域，从而逐渐限制细胞命运。我们利用果蝇眼睛模型来了解负责确定腹侧边缘眼睛和头部表皮之间边界的遗传回路。早期眼睛的默认状态是腹侧的，并且取决于Lobe（L）和Notch配体Serrate（Ser）的功能。我们鉴定出homothorax（hth）是腹侧眼缺失的L突变体表型的一个强效增强子。Hth是一个MEIS类基因，具有高度保守的Meis - Hth（MH）结构域和一个同源结构域（HD）。已知Hth通过其MH结构域与Extradenticle（Exd）结合以实现其核转位。作为眼睛的负调控因子，hth的功能缺失会导致腹侧眼异位增大。这种表型与腹侧眼缺失的L突变体表型互补。然而，L和hth在腹侧眼发育过程中是否相互作用仍然未知。在此我们表明：（i）L对hth起拮抗作用；（ii）在L突变体背景下Hth上调；（iii）Hth的MH结构域是其与L发生遗传相互作用所必需的，而其同源结构域则不是；（iv）在L突变体背景下，Hth的腹侧眼抑制功能涉及新的依赖于MH结构域的因子；（v）Exd的核定位不足以介导L突变体背景下的Hth功能。此外，Exd不是Hth功能的关键限速因子。因此，需要L和Hth的最佳水平来确定发育中的眼睛和腹侧边缘头部表皮之间的边界。