Kambadur R, Koizumi K, Stivers C, Nagle J, Poole S J, Odenwald W F
The Neurogenetics Unit, Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland 20892 USA.
Genes Dev. 1998 Jan 15;12(2):246-60. doi: 10.1101/gad.12.2.246.
POU transcription factors participate in cell-identity decisions during nervous system development, yet little is known about the regulatory networks controlling their expression. We report all known Drosophila POU genes require castor (cas) for correct CNS expression. drifter and I-POU depend on cas for full expression, whereas pdm-1 and pdm-2 are negatively regulated. cas encodes a zinc finger protein that shares DNA-binding specificity with another pdm repressor: the gap segmentation gene regulator Hunchback (Hb). Our studies reveal that the embryonic CNS contains sequentially generated neuroblast sublineages that can be distinguished by their expression of either Hb, Pdm-1, or Cas. Hb and Cas may directly silence pdm expression in early and late developing sublineages, given that pdm-1 cis-regulatory DNA contains >=32 Hb/Cas-binding sites and its enhancer(s) are ectopically activated in cas- neuroblasts. In addition, the targeted misexpression of Cas in all neuroblast lineages reduces Pdm-1 expression without altering Hb expression. By ensuring correct POU gene expression boundaries, hb and cas maintain temporal subdivisions in the cell-identity circuitry controlling CNS development.
POU转录因子在神经系统发育过程中参与细胞身份的决定,但对于控制其表达的调控网络却知之甚少。我们报告,所有已知的果蝇POU基因在中枢神经系统(CNS)中的正确表达都需要蓖麻蛋白(cas)。漂流者基因(drifter)和I-POU基因的充分表达依赖于cas,而pdm-1和pdm-2则受到负调控。cas编码一种锌指蛋白,它与另一种pdm阻遏物——间隙分割基因调节因子驼背蛋白(Hb)具有相同的DNA结合特异性。我们的研究表明,胚胎中枢神经系统包含依次产生的神经母细胞亚系,这些亚系可以通过它们对Hb、Pdm-1或Cas的表达来区分。鉴于pdm-1顺式调控DNA包含≥32个Hb/Cas结合位点,并且其增强子在缺乏cas的神经母细胞中异位激活,因此Hb和Cas可能在早期和晚期发育的亚系中直接沉默pdm的表达。此外,在所有神经母细胞谱系中靶向错误表达Cas会降低Pdm-1的表达,而不会改变Hb的表达。通过确保正确的POU基因表达边界,hb和cas在控制中枢神经系统发育的细胞身份电路中维持时间上的细分。