Hirono Keiko, Kohwi Minoree, Clark Matt Q, Heckscher Ellie S, Doe Chris Q
Howard Hughes Medical Institute, Eugene, 97403, USA.
Institute of Molecular Biology, Eugene, 97403, USA.
Neural Dev. 2017 Jan 31;12(1):1. doi: 10.1186/s13064-017-0078-1.
Drosophila and mammalian neural progenitors typically generate a diverse family of neurons in a stereotyped order. Neuronal diversity can be generated by the sequential expression of temporal transcription factors. In Drosophila, neural progenitors (neuroblasts) sequentially express the temporal transcription factors Hunchback (Hb), Kruppel, Pdm, and Castor. Hb is necessary and sufficient to specify early-born neuronal identity in multiple lineages, and is maintained in the post-mitotic neurons produced during each neuroblast expression window. Surprisingly, nothing is currently known about whether Hb acts in neuroblasts or post-mitotic neurons (or both) to specify first-born neuronal identity.
Here we selectively remove Hb from post-mitotic neurons, and assay the well-characterized NB7-1 and NB1-1 lineages for defects in neuronal identity and function.
We find that loss of Hb from embryonic and larval post-mitotic neurons does not affect neuronal identity. Furthermore, removing Hb from post-mitotic neurons throughout the entire CNS has no effect on larval locomotor velocity, a sensitive assay for motor neuron and pre-motor neuron function.
We conclude that Hb functions in progenitors (neuroblasts/GMCs) to establish heritable neuronal identity that is maintained by a Hb-independent mechanism. We suggest that Hb acts in neuroblasts to establish an epigenetic state that is permanently maintained in early-born neurons.
果蝇和哺乳动物的神经祖细胞通常以固定顺序产生多种类型的神经元。神经元多样性可通过时序转录因子的顺序表达产生。在果蝇中,神经祖细胞(神经母细胞)依次表达时序转录因子驼背蛋白(Hb)、克鲁佩尔、Pdm和蓖麻蛋白。Hb对于指定多个谱系中早期生成的神经元身份是必要且充分的,并且在每个神经母细胞表达窗口期间产生的有丝分裂后神经元中得以维持。令人惊讶的是,目前对于Hb是在神经母细胞还是有丝分裂后神经元(或两者都有)中起作用以指定首个生成的神经元身份一无所知。
在此,我们选择性地从有丝分裂后神经元中去除Hb,并检测特征明确的NB7-1和NB1-1谱系在神经元身份和功能方面的缺陷。
我们发现从胚胎期和幼虫期有丝分裂后神经元中去除Hb并不影响神经元身份。此外,在整个中枢神经系统的有丝分裂后神经元中去除Hb对幼虫运动速度没有影响,而幼虫运动速度是检测运动神经元和运动前神经元功能的灵敏指标。
我们得出结论,Hb在祖细胞(神经母细胞/神经胶质母细胞)中发挥作用以建立可遗传的神经元身份,该身份通过一种不依赖Hb的机制得以维持。我们认为Hb在神经母细胞中发挥作用以建立一种表观遗传状态,该状态在早期生成的神经元中永久维持。