Notch signaling via Hes1 transcription factor maintains survival of melanoblasts and melanocyte stem cells.

Melanoblasts (Mbs) are thought to be strictly regulated by cell–cell interactions with epidermal keratinocytes, although the precise molecular mechanism of the regulation has been elusive. Notch signaling, whose activation is mediated by cell–cell interactions, is implicated in a broad range of developmental processes. We demonstrate the vital role of Notch signaling in the maintenance of Mbs, as well as melanocyte stem cells (MSCs). Conditional ablation of Notch signaling in the melanocyte lineage leads to a severe defect in hair pigmentation, followed by intensive hair graying. The defect is caused by a dramatic elimination of Mbs and MSCs. Furthermore, targeted overexpression of Hes1 is sufficient to protect Mbs from the elimination by apoptosis. Thus, these data provide evidence that Notch signaling, acting through Hes1, plays a crucial role in the survival of immature Mbs by preventing initiation of apoptosis.

黑素母细胞（Mbs）被认为受到与表皮角质形成细胞的细胞 - 细胞相互作用的严格调控，尽管这种调控的确切分子机制一直难以捉摸。Notch信号传导由细胞 - 细胞相互作用介导其激活，涉及广泛的发育过程。我们证明了Notch信号在黑素母细胞以及黑素细胞干细胞（MSCs）的维持中起着至关重要的作用。在黑素细胞谱系中条件性地消除Notch信号会导致毛发色素沉着的严重缺陷，进而出现严重的毛发变白现象。这种缺陷是由黑素母细胞和黑素细胞干细胞的大量缺失所导致的。此外，Hes1的靶向过表达足以保护黑素母细胞免于因凋亡而被清除。因此，这些数据提供了证据，表明Notch信号通过Hes1发挥作用，通过阻止凋亡的启动在未成熟黑素母细胞的存活中起着关键作用。