Gilboa Lilach, Lehmann Ruth
Howard Hughes Medical Institute and Developmental Genetics Program, The Skirball Institute and Department of Cell Biology, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.
Nature. 2006 Sep 7;443(7107):97-100. doi: 10.1038/nature05068. Epub 2006 Aug 27.
The ability of organs such as the liver or the lymphoid system to maintain their original size or regain it after injury is well documented. However, little is known about how these organs sense that equilibrium is breached, and how they cease changing when homeostasis is reached. Similarly, it remains unclear how, during normal development, different cell types within an organ coordinate their growth. Here we show that during gonad development in the fruitfly Drosophila melanogaster the proliferation of primordial germ cells (PGCs) and survival of the somatic intermingled cells (ICs) that contact them are coordinated by means of a feedback mechanism composed of a positive signal and a negative signal. PGCs express the EGF receptor (EGFR) ligand Spitz, which is required for IC survival. In turn, ICs inhibit PGC proliferation. Thus, homeostasis and coordination of growth between soma and germ line in the larval ovary is achieved by using a sensor of PGC numbers (EGFR-mediated survival of ICs) coupled to a correction mechanism inhibiting PGC proliferation. This feedback loop ensures that sufficient numbers of PGCs exist to fill all the stem-cell niches that form at the end of larval development. We propose that similar feedback mechanisms might be generally used for coordinated growth, regeneration and homeostasis.
肝脏或淋巴系统等器官在受伤后维持其原始大小或恢复原状的能力已有充分记录。然而,对于这些器官如何感知平衡被打破,以及在达到稳态时如何停止变化,我们却知之甚少。同样,在正常发育过程中,器官内不同细胞类型如何协调其生长也仍不清楚。在此,我们表明,在果蝇黑腹果蝇的性腺发育过程中,原始生殖细胞(PGC)的增殖以及与其接触的体细胞混合细胞(IC)的存活是通过一种由正信号和负信号组成的反馈机制来协调的。PGC表达表皮生长因子受体(EGFR)配体Spitz,这是IC存活所必需的。反过来,IC会抑制PGC的增殖。因此,通过使用PGC数量的传感器(EGFR介导的IC存活)与抑制PGC增殖的校正机制相结合,实现了幼虫卵巢中体细胞和生殖系之间的稳态及生长协调。这个反馈回路确保有足够数量的PGC来填充幼虫发育末期形成的所有干细胞微环境。我们提出,类似的反馈机制可能普遍用于协调生长、再生和稳态。