Binary Switching of Calendar Cells in the Pituitary Defines the Phase of the Circannual Cycle in Mammals.
Binary Switching of Calendar Cells in the Pituitary Defines the Phase of the Circannual Cycle in Mammals.
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DOI：
10.1016/j.cub.2015.09.014
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发表时间：
2015-10-19
期刊：
影响因子：
--
通讯作者：
Loudon AS
中科院分区：
文献类型：
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作者：
Wood SH;Christian HC;Miedzinska K;Saer BR;Johnson M;Paton B;Yu L;McNeilly J;Davis JR;McNeilly AS;Burt DW;Loudon AS
动物进化出了持续的自由运行的年周期（大约一年之久）节律，以调节激素周期，驱动代谢节律（包括冬眠），并确定每年繁殖的时间。最近的研究已经定义了光周期输入到这个节奏，其中褪黑激素作用于垂体结节部（PT）的促甲状腺细胞，导致下丘脑中甲状腺激素代谢控制的季节性变化。然而，在许多物种中，在没有变化的光周期信号的情况下，季节节律在恒定的条件下持续存在，从而导致产生年周期。目前尚不清楚是哪些细胞、组织和途径产生了这些显著的长期节律过程。我们发现，个人PT促甲状腺激素细胞可以在两个二元状态之一，反映了长（EYA 3+）或短（CHGA+）光周期，在每个状态的相对比例定义的阶段的circannual周期。我们还表明，形态发生周期驱动的PT导致广泛的重建PT和下丘脑在circannual周期。我们认为，PT可能采用概括的发育途径，以驱动组织和细胞的形态变化。我们的数据是一致的假设，circannual计时器可能驻留在PT促甲状腺细胞和编码的二进制开关定时机制，这可能会调节产生的circannual神经内分泌节律，导致动态重建的下丘脑接口。总之，PT-腹侧下丘脑现在似乎是一个主要的结构参与长期的节奏的产生。一个年周期计时器可能存在于垂体结节部促甲状腺激素细胞中，这是由控制EYA 3表达的数字开关机制定义的。年周期时钟驱动PT和下丘脑的形态发生周期，这涉及发育程序的重演。年周期节律已经进化为调节和计时生理学的年度变化。Wood等人报告称，结节部通过EYA 3表达的数字转换产生哺乳动物的昼夜节律。一个概括的发展途径是由昼夜时钟驱动PT和下丘脑的形态发生周期。
Persistent free-running circannual (approximately year-long) rhythms have evolved in animals to regulate hormone cycles, drive metabolic rhythms (including hibernation), and time annual reproduction. Recent studies have defined the photoperiodic input to this rhythm, wherein melatonin acts on thyrotroph cells of the pituitary pars tuberalis (PT), leading to seasonal changes in the control of thyroid hormone metabolism in the hypothalamus. However, seasonal rhythms persist in constant conditions in many species in the absence of a changing photoperiod signal, leading to the generation of circannual cycles. It is not known which cells, tissues, and pathways generate these remarkable long-term rhythmic processes. We show that individual PT thyrotrophs can be in one of two binary states reflecting either a long (EYA3+) or short (CHGA+) photoperiod, with the relative proportion in each state defining the phase of the circannual cycle. We also show that a morphogenic cycle driven by the PT leads to extensive re-modeling of the PT and hypothalamus over the circannual cycle. We propose that the PT may employ a recapitulated developmental pathway to drive changes in morphology of tissues and cells. Our data are consistent with the hypothesis that the circannual timer may reside within the PT thyrotroph and is encoded by a binary switch timing mechanism, which may regulate the generation of circannual neuroendocrine rhythms, leading to dynamic re-modeling of the hypothalamic interface. In summary, the PT-ventral hypothalamus now appears to be a prime structure involved in long-term rhythm generation. A circannual timer may reside in the pituitary pars tuberalis thyrotroph This is defined by a digital switching mechanism controlling EYA3 expression The circannual clockwork drives a morphogenic cycle in the PT and hypothalamus This involves recapitulation of a developmental program Circannual rhythms have evolved to regulate and time annual changes in physiology. Wood et al. report that the pars tuberalis generates the circannual rhythm in mammals through the digital switching of EYA3 expression. A recapitulated developmental pathway is used by the circannual clock to drive a morphogenic cycle in the PT and hypothalamus.