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      • Opposing interactions between <i>homothorax</i> and <i>Lobe</i> define the ventral eye margin of <i>Drosophila</i> eye

        Singh, Amit,Tare, Meghana,Kango-Singh, Madhuri,Son, Won-Seok,Cho, Kyung-Ok,Choi, Kwang-wook Elsevier 2011 Developmental biology Vol.359 No.2

        <P><B>Abstract</B></P><P>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 <I>Drosophila</I> 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 <I>Lobe (L)</I> and the Notch ligand <I>Serrate (Ser)</I>. We identified <I>homothorax (hth)</I> as a strong enhancer of the <I>L</I> 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 <I>hth</I>, a negative regulator of eye, results in ectopic ventral eye enlargements. This phenotype is complementary to the <I>L</I> mutant phenotype of loss-of-ventral eye. However, if <I>L</I> and <I>hth</I> interact during ventral eye development remains unknown. Here we show that (i) <I>L</I> acts antagonistically to <I>hth</I>, (ii) Hth is upregulated in the <I>L</I> mutant background, and (iii) MH domain of Hth is required for its genetic interaction with L, while its homeodomain is not, (iv) in <I>L</I> mutant background ventral eye suppression function of Hth involves novel MH domain-dependent factor(s), and (v) nuclear localization of Exd is not sufficient to mediate the Hth function in the <I>L</I> 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.</P> <P><B>Highlights</B></P><P>► We study the genetic mechanism involved in generation of head versus eye boundary during organogenesis in flies. ► <I>homothorax (hth)</I> acts antagonistically to the <I>Lobe</I> (<I>L</I>, PRAS40 homolog) in the ventral eye. ► L interacts with alternative spliced variant of Hth that encodes Meis-Hth (MH) domain. ► Optimum level of <I>L</I> and <I>hth</I> define boundary between eye and the head cuticle on ventral margin. ► Extradenticle (Exd) is not a critical rate limiting factor in L and Hth interaction.</P>

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