In mammals, the circadian clock network drives daily rhythms of tissue-specific homeostasis. To dissect daily inter-tissue communication, we constructed a mouse minimal clock network comprising only two nodes: the peripheral epidermal clock and the central brain clock. By transcriptomic and functional characterization of this isolated connection, we identified a gatekeeping function of the peripheral tissue clock with respect to systemic inputs. The epidermal clock concurrently integrates and subverts brain signals to ensure timely execution of epidermal daily physiology. Timely cell-cycle termination in the epidermal stem cell compartment depends upon incorporation of clock-driven signals originating from the brain. In contrast, the epidermal clock corrects or outcompetes potentially disruptive feeding-related signals to ensure the optimal timing of DNA replication. Together, we present an approach for cataloging the systemic dependencies of daily temporal organization in a tissue and identify an essential gate-keeping function of peripheral circadian clocks that guarantees tissue homeostasis.

在哺乳动物中，生物钟网络驱动着组织特异性稳态的日常节律。为了剖析日常组织间通讯，我们构建了一个小鼠最小时钟网络，仅包含两个节点：外周表皮时钟和中央大脑时钟。通过这种孤立连接的转录组学和功能表征，我们确定了外周组织时钟相对于系统输入的看门功能。表皮时钟同时整合和颠覆大脑信号，以确保表皮日常生理的及时执行。表皮干细胞室中细胞周期的及时终止取决于来自大脑的时钟驱动信号的结合。相比之下，表皮时钟会纠正或击败潜在的破坏性进食相关信号，以确保 DNA 复制的最佳时机。我们共同提出了一种对组织中日常时间组织的系统依赖性进行分类的方法，并确定了保证组织稳态的外周生物钟的基本守门功能。