Department of Anatomy and Regenerative Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA.
GW Cancer Center, George Washington University School of Medicine and Health Sciences, Washington, DC, 20052, USA.
Nat Commun. 2017 Nov 2;8(1):1275. doi: 10.1038/s41467-017-01364-z.
The Drosophila Hedgehog receptor functions to regulate the essential downstream pathway component, Smoothened, and to limit the range of signaling by sequestering Hedgehog protein signal within imaginal disc epithelium. Hedgehog receptor function requires both Patched and Ihog activity, the latter interchangeably encoded by interference hedgehog (ihog) or brother of ihog (boi). Here we show that Patched and Ihog activity are mutually required for receptor endocytosis and degradation, triggered by Hedgehog protein binding, and causing reduced levels of Ihog/Boi proteins in a stripe of cells at the anterior/posterior compartment boundary of the wing imaginal disc. This Ihog spatial discontinuity may contribute to classically defined cell segregation and lineage restriction at the anterior/posterior wing disc compartment boundary, as suggested by our observations that Ihog activity mediates aggregation of otherwise non-adherent cultured cells and that loss of Ihog activity disrupts wing disc cell segregation, even with downstream genetic rescue of Hedgehog signal response.
果蝇 Hedgehog 受体的功能是调节重要的下游途径成分 Smoothened，并通过将 Hedgehog 蛋白信号隔离在 imaginal 盘上皮组织内来限制信号传递范围。Hedgehog 受体功能需要 Patched 和 Ihog 活性，后者由干扰 Hedgehog（ihog）或 ihog 的兄弟（boi）编码。在这里，我们表明，Patched 和 Ihog 活性相互需要，用于 Hedgehog 蛋白结合触发的受体内吞和降解，导致 Wing imaginal disc 前/后隔室边界处的细胞条纹中 Ihog/BoI 蛋白水平降低。这种 Ihog 空间不连续性可能有助于在前/后翅盘隔室边界处经典定义的细胞分离和谱系限制，正如我们的观察结果所表明的那样，Ihog 活性介导了原本不粘附的培养细胞的聚集，并且即使下游 Hedgehog 信号反应的遗传挽救也会破坏 Wing disc 细胞分离。
