Klebanow Lindsey R, Peshel Emanuela C, Schuster Andrew T, De Kuntal, Sarvepalli Kavitha, Lemieux Madeleine E, Lenoir Jessica J, Moore Adrian W, McDonald Jocelyn A, Longworth Michelle S
Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Bioinfo, Plantagenet, ON K0B 1L0, Canada.
Development. 2016 Aug 1;143(15):2791-802. doi: 10.1242/dev.133686. Epub 2016 Jun 17.
The pattern of the Drosophila melanogaster adult wing is heavily influenced by the expression of proteins that dictate cell fate decisions between intervein and vein during development. dSRF (Blistered) expression in specific regions of the larval wing disc promotes intervein cell fate, whereas EGFR activity promotes vein cell fate. Here, we report that the chromatin-organizing protein CAP-D3 acts to dampen dSRF levels at the anterior/posterior boundary in the larval wing disc, promoting differentiation of cells into the anterior crossvein. CAP-D3 represses KNOT expression in cells immediately adjacent to the anterior/posterior boundary, thus blocking KNOT-mediated repression of EGFR activity and preventing cell death. Maintenance of EGFR activity in these cells depresses dSRF levels in the neighboring anterior crossvein progenitor cells, allowing them to differentiate into vein cells. These findings uncover a novel transcriptional regulatory network influencing Drosophila wing vein development, and are the first to identify a Condensin II subunit as an important regulator of EGFR activity and cell fate determination in vivo.
果蝇成虫翅膀的图案受到蛋白质表达的严重影响,这些蛋白质在发育过程中决定了翅脉间和翅脉细胞命运的抉择。幼虫翅盘特定区域中的dSRF(起泡)表达促进翅脉间细胞命运,而表皮生长因子受体(EGFR)活性促进翅脉细胞命运。在此,我们报告染色质组织蛋白CAP-D3在幼虫翅盘中的前后边界处降低dSRF水平,促进细胞分化为前交叉翅脉。CAP-D3抑制紧邻前后边界的细胞中的KNOT表达,从而阻断KNOT介导的对EGFR活性的抑制并防止细胞死亡。这些细胞中EGFR活性的维持会降低相邻的前交叉翅脉祖细胞中的dSRF水平,使其能够分化为翅脉细胞。这些发现揭示了一个影响果蝇翅脉发育的新型转录调控网络,并且首次确定凝聚素II亚基是体内EGFR活性和细胞命运决定的重要调节因子。