Kimmel Center for Biology and Medicine of the Skirball Institute, NYU School of Medicine, Department of Cell Biology, 540 First Avenue, New York, NY 10016, USA.
Development. 2010 Jan;137(2):273-81. doi: 10.1242/dev.041244.
Development involves the establishment of boundaries between fields specified to differentiate into distinct tissues. The Drosophila larval eye-antennal imaginal disc must be subdivided into regions that differentiate into the adult eye, antenna and head cuticle. We have found that the transcriptional co-factor Chip is required for cells at the ventral eye-antennal disc border to take on a head cuticle fate; clones of Chip mutant cells in this region instead form outgrowths that differentiate into ectopic eye tissue. Chip acts independently of the transcription factor Homothorax, which was previously shown to promote head cuticle development in the same region. Chip and its vertebrate CLIM homologues have been shown to form complexes with LIM-homeodomain transcription factors, and the domain of Chip that mediates these interactions is required for its ability to suppress the eye fate. We show that two LIM-homeodomain proteins, Arrowhead and Lim1, are expressed in the region of the eye-antennal disc affected in Chip mutants, and that both require Chip for their ability to suppress photoreceptor differentiation when misexpressed in the eye field. Loss-of-function studies support the model that Arrowhead and Lim1 act redundantly, using Chip as a co-factor, to prevent retinal differentiation in regions of the eye disc destined to become ventral head tissue.
发育涉及到指定领域的边界的建立,以分化为不同的组织。果蝇幼虫眼触角体节盘必须被细分为区域,分化为成虫眼、触角和头部表皮。我们发现,转录共因子 Chip 对于位于眼触角盘腹侧边界的细胞获得头部表皮命运是必需的;该区域 Chip 突变细胞的克隆形成向外生长,分化为异位眼组织。Chip 独立于转录因子 Homothorax 发挥作用,后者先前被证明在同一区域促进头部表皮的发育。Chip 及其脊椎动物 CLIM 同源物已被证明与 LIM 同源域转录因子形成复合物,并且介导这些相互作用的 Chip 结构域对于其抑制眼睛命运的能力是必需的。我们表明,两种 LIM 同源域蛋白,Arrowhead 和 Lim1,在 Chip 突变体中受影响的眼触角盘区域表达,并且当在眼区域异位表达时,它们都需要 Chip 来抑制光感受器分化。功能丧失研究支持 Arrowhead 和 Lim1 冗余地作用的模型,利用 Chip 作为共因子,防止眼盘的注定成为腹侧头部组织的区域发生视网膜分化。