Lu Wen, Lakonishok Margot, Gelfand Vladimir I
Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
bioRxiv. 2023 Mar 10:2023.03.09.531953. doi: 10.1101/2023.03.09.531953.
In many species, only one oocyte is specified among a group of interconnected germline sister cells. In , 16-cell interconnected cells form a germline cyst, where one cell differentiates into an oocyte, while the rest become nurse cells that supply the oocyte with mRNAs, proteins, and organelles through intercellular cytoplasmic bridges named ring canals via microtubule-based transport. In this study, we find that a microtubule polymerase Mini spindles (Msps), the homolog of XMAP215, is essential for the oocyte fate determination. mRNA encoding Msps is concentrated in the oocyte by dynein-dependent transport along microtubules. Translated Msps stimulates microtubule polymerization in the oocyte, causing more microtubule plus ends to grow from the oocyte through the ring canals into nurse cells, further enhancing nurse cell-to-oocyte transport by dynein. Knockdown of blocks the oocyte growth and causes gradual loss of oocyte determinants. Thus, the Msps-dynein duo creates a positive feedback loop, enhancing dynein-dependent nurse cell-to-oocyte transport and transforming a small stochastic difference in microtubule polarity among sister cells into a clear oocyte fate determination.
Oocyte determination in provides a valuable model for studying cell fate specification. We describe the crucial role of the duo of microtubule polymerase Mini spindles (Msps) and cytoplasmic dynein in this process. We show that Msps is essential for oocyte fate determination. Msps concentration in the oocyte is achieved through dynein-dependent transport of mRNA along microtubules. Translated Msps stimulates microtubule polymerization in the oocyte, further enhancing nurse cell-to-oocyte transport by dynein. This creates a positive feedback loop that transforms a small stochastic difference in microtubule polarity among sister cells into a clear oocyte fate determination. Our findings provide important insights into the mechanisms of oocyte specification and have implications for understanding the development of multicellular organisms.
在许多物种中,一组相互连接的生殖系姐妹细胞中只有一个卵母细胞被指定。在果蝇中,16个相互连接的细胞形成一个生殖系囊肿,其中一个细胞分化为卵母细胞,其余细胞则成为营养细胞,通过名为环管的细胞间胞质桥,经基于微管的运输为卵母细胞提供mRNA、蛋白质和细胞器。在本研究中,我们发现微管聚合酶小纺锤体(Msps),即XMAP215的同源物,对于卵母细胞命运的决定至关重要。编码Msps的mRNA通过动力蛋白沿微管的依赖性运输集中在卵母细胞中。翻译后的Msps刺激卵母细胞中的微管聚合,导致更多微管正端从卵母细胞通过环管生长到营养细胞中,进一步增强动力蛋白介导的从营养细胞到卵母细胞的运输。敲低Msps会阻碍卵母细胞生长并导致卵母细胞决定因素逐渐丧失。因此,Msps-动力蛋白组合形成了一个正反馈回路,增强了动力蛋白介导的从营养细胞到卵母细胞的运输,并将姐妹细胞之间微管极性的微小随机差异转化为明确的卵母细胞命运决定。
果蝇中的卵母细胞决定为研究细胞命运特化提供了一个有价值的模型。我们描述了微管聚合酶小纺锤体(Msps)和细胞质动力蛋白组合在这一过程中的关键作用。我们表明Msps对于卵母细胞命运决定至关重要。Msps在卵母细胞中的富集是通过动力蛋白沿微管对Msps mRNA的依赖性运输实现的。翻译后的Msps刺激卵母细胞中的微管聚合,进一步增强动力蛋白介导的从营养细胞到卵母细胞的运输。这形成了一个正反馈回路,将姐妹细胞之间微管极性的微小随机差异转化为明确的卵母细胞命运决定。我们的发现为卵母细胞特化机制提供了重要见解,并对理解多细胞生物的发育具有启示意义。