De Iaco Rossana, Soustelle Laurent, Kammerer Martial, Sorrentino Sandro, Jacques Cécile, Giangrande Angela
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch Cedex, CU de Strasbourg, France.
EMBO J. 2006 Jan 11;25(1):244-54. doi: 10.1038/sj.emboj.7600907. Epub 2005 Dec 15.
Cell specification in the nervous system requires patterning genes dictating spatio-temporal coordinates as well as fate determinants. In the case of neurons, which are controlled by the family of proneural transcription factors, binding specificity and patterned expression trigger both differentiation and specification. In contrast, a single gene, glide cell deficient/glial cell missing (glide/gcm), is sufficient for all fly lateral glial differentiation. How can different types of cells develop in the presence of a single fate determinant, that is, how do differentiation and specification pathways integrate and produce distinct glial populations is not known. By following an identified lineage, we here show that glia specification is triggered by high glide/gcm expression levels, mediated by cell-specific protein-protein interactions. Huckebein (Hkb), a lineage-specific factor, provides a molecular link between glide/gcm and positional cues. Importantly, Hkb does not activate transcription; rather, it physically interacts with Glide/Gcm thereby triggering its autoregulation. These data emphasize the importance of fate determinant cell-specific quantitative regulation in the establishment of cell diversity.
神经系统中的细胞特化需要模式基因来决定时空坐标以及命运决定因子。就由神经前体转录因子家族控制的神经元而言，结合特异性和模式化表达会触发分化和特化。相比之下，单个基因，即滑行细胞缺陷/胶质细胞缺失（glide/gcm），就足以驱动所有果蝇侧胶质细胞的分化。在存在单一命运决定因子的情况下，不同类型的细胞如何发育，也就是说，分化和特化途径如何整合并产生不同的胶质细胞群体，目前尚不清楚。通过追踪一个已确定的谱系，我们在此表明，胶质细胞特化是由高表达水平的glide/gcm触发的，这是由细胞特异性蛋白质-蛋白质相互作用介导的。哈克贝恩（Hkb），一种谱系特异性因子，在glide/gcm和位置线索之间提供了分子联系。重要的是，Hkb并不激活转录；相反，它与Glide/Gcm发生物理相互作用，从而触发其自身调节。这些数据强调了命运决定因子细胞特异性定量调节在细胞多样性建立中的重要性。
