Institute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, Singapore 138673, Singapore.
Institute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, Singapore 138673, Singapore; Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119288, Singapore; Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
Dev Biol. 2018 Nov 15;443(2):165-172. doi: 10.1016/j.ydbio.2018.09.013. Epub 2018 Sep 12.
Multiciliated cells (MCCs) differentiate arrays of motile cilia that beat to drive fluid flow over epithelia. Recent studies have established two Geminin family coiled-coil containing nuclear regulatory proteins, Gmnc and Multicilin (Mci), in the specification and differentiation of the MCCs. Both Gmnc and Mci are devoid of a DNA binding domain: they regulate transcription by associating with E2f family transcription factors, notably E2f4 and E2f5. Here, we have studied the relative contribution of these two E2f factors in MCC development using the zebrafish embryo, which differentiates MCCs within kidney tubules and the nose. We found that while E2f4 is fully dispensable, E2f5 is essential for MCCs to form in the kidney tubules. Moreover, using a variety of double mutant combinations we show that E2f5 has a more prominent role in MCC development in the zebrafish than E2f4. This contrasts with current evidence from the mouse, where E2f4 seems to be more important. Thus, distinct combinatorial activities of the E2f4 and E2f5 proteins regulate the specification and differentiation of MCCs in zebrafish and mice.
纤毛细胞（MCCs）分化为运动纤毛的阵列，这些纤毛的摆动驱动上皮细胞上的液体流动。最近的研究已经确定了两个 Geminin 家族的螺旋-环-螺旋核调节蛋白，Gmnc 和 Multicilin（Mci），在 MCCs 的特化和分化中发挥作用。Gmnc 和 Mci 都缺乏 DNA 结合域：它们通过与 E2f 家族转录因子，特别是 E2f4 和 E2f5，结合来调节转录。在这里，我们使用斑马鱼胚胎研究了这两个 E2f 因子在 MCC 发育中的相对贡献，斑马鱼胚胎在肾脏小管和鼻子中分化出 MCCs。我们发现，虽然 E2f4 是完全可有可无的，但 E2f5 对于肾脏小管中 MCCs 的形成是必不可少的。此外，通过多种双突变体组合，我们表明 E2f5 在斑马鱼中对 MCC 发育的作用比 E2f4 更为突出。这与来自小鼠的当前证据形成对比，在小鼠中，E2f4 似乎更为重要。因此，E2f4 和 E2f5 蛋白的不同组合活性调节了斑马鱼和小鼠中 MCCs 的特化和分化。
