Chang Ting, Shy Diana, Hartenstein Volker
Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA.
Dev Biol. 2003 Nov 1;263(1):103-13. doi: 10.1016/s0012-1606(03)00448-2.
The Drosophila eye field that gives rise to the visual system and dorsal head epidermis forms an unpaired anlage located in the dorsal head ectoderm. The eye field expresses and requires both Dpp and EGFR signaling for its development. As shown in previous studies, EGFR is required for cell maintenance in the developing visual system. Dpp initially switches on the early eye genes so and eya in the eye field. Consecutively, high levels of Dpp in the dorsal midline inhibit these genes and promote development of head epidermis. We show that Dpp negatively regulates EGFR signaling, thereby increasing the amount of cell death in the dorsal midline. By this mechanism, Dpp controls the formation of a bilateral visual system and indirectly modulates cell death, which is essential for normal head morphogenesis. Loss of either Dpp or its downstream target, Zen, abolishes head epidermis fate and leads to the misexpression of dp-ERK in the dorsal midline. The resulting morphological phenotype consists of cyclopia, reduction of cell death, and failure of head involution. Ectopic expression of activated EGFR inhibits the Dpp target race and thereby causes cyclopia and defective head involution. We discuss possible mechanisms of Dpp and EGFR interaction in the embryo.
产生视觉系统和头部背侧表皮的果蝇眼场形成一个位于头部背侧外胚层的不成对原基。眼场在其发育过程中表达并需要Dpp和EGFR信号传导。如先前研究所示，EGFR是发育中的视觉系统中细胞维持所必需的。Dpp最初开启眼场中的早期眼基因so和eya。随后，背中线中高水平的Dpp抑制这些基因并促进头部表皮的发育。我们发现Dpp负向调节EGFR信号传导，从而增加背中线中的细胞死亡量。通过这种机制，Dpp控制双侧视觉系统的形成并间接调节细胞死亡，这对于正常的头部形态发生至关重要。Dpp或其下游靶标Zen的缺失消除了头部表皮命运，并导致背中线中dp-ERK的错误表达。由此产生的形态学表型包括独眼畸形、细胞死亡减少和头部内卷失败。活化EGFR的异位表达抑制Dpp靶标race，从而导致独眼畸形和有缺陷的头部内卷。我们讨论了胚胎中Dpp和EGFR相互作用的可能机制。
