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唇基因在果蝇脑的胚胎后发育中被要求终止已鉴定的神经母细胞的增殖。

The labial gene is required to terminate proliferation of identified neuroblasts in postembryonic development of the Drosophila brain.

机构信息

Biozentrum, University of Basel , CH 4056 Basel , Switzerland.

出版信息

Biol Open. 2012 Oct 15;1(10):1006-15. doi: 10.1242/bio.20121966. Epub 2012 Aug 17.

Abstract

The developing brain of Drosophila has become a useful model for studying the molecular genetic mechanisms that give rise to the complex neuronal arrays that characterize higher brains in other animals including mammals. Brain development in Drosophila begins during embryogenesis and continues during a subsequent postembryonic phase. During embryogenesis, the Hox gene labial is expressed in the developing tritocerebrum, and labial loss-of-function has been shown to be associated with a loss of regional neuronal identity and severe patterning defects in this part of the brain. However, nothing is known about the expression and function of labial, or any other Hox gene, during the postembryonic phase of brain development, when the majority of the neurons in the adult brain are generated. Here we report the first analysis of Hox gene action during postembryonic brain development in Drosophila. We show that labial is expressed initially in six larval brain neuroblasts, of which only four give rise to the labial expressing neuroblast lineages present in the late larval brain. Although MARCM-based clonal mutation of labial in these four neuroblast lineages does not result in an obvious phenotype, a striking and unexpected effect of clonal labial loss-of-function does occur during postembryonic brain development, namely the formation of two ectopic neuroblast lineages that are not present in wildtype brains. The same two ectopic neuroblast lineages are also observed following cell death blockage and, significantly, in this case the resulting ectopic lineages are Labial-positive. These findings imply that labial is required in two specific neuroblast lineages of the wildtype brain for the appropriate termination of proliferation through programmed cell death. Our analysis of labial function reveals a novel cell autonomous role of this Hox gene in shaping the lineage architecture of the brain during postembryonic development.

摘要

果蝇的大脑发育已成为研究产生复杂神经元阵列的分子遗传机制的有用模型,这些神经元阵列是其他动物(包括哺乳动物)高级大脑的特征。果蝇的大脑发育始于胚胎发生期,并在随后的胚胎后阶段继续进行。在胚胎发生期间,Hox 基因 labial 在发育中的 Tritocerebrum 中表达,并且已经证明 labial 功能丧失与该脑区的区域神经元身份丧失和严重的模式缺陷有关。但是,在成年大脑中产生的大多数神经元产生的胚胎后大脑发育阶段,尚不知道 labial 或任何其他 Hox 基因的表达和功能。在这里,我们报告了在果蝇胚胎后大脑发育过程中首次分析 Hox 基因作用的结果。我们表明,labial 最初在六个幼虫脑神经母细胞中表达,其中只有四个产生存在于晚期幼虫脑中的 labial 表达神经母细胞谱系。尽管基于 MARCM 的 labial 在这四个神经母细胞谱系中的克隆突变不会导致明显的表型,但在胚胎后大脑发育过程中,克隆 labial 功能丧失会产生惊人且出乎意料的影响,即形成两个不在野生型大脑中存在的异位神经母细胞谱系。在胚胎后大脑发育过程中,还观察到相同的两个异位神经母细胞谱系,并且在细胞死亡阻断后也观察到,重要的是,在这种情况下,产生的异位谱系是 Labial 阳性的。这些发现意味着 labial 在野生型大脑中的两个特定神经母细胞谱系中是必需的,以便通过程序性细胞死亡适当终止增殖。我们对 labial 功能的分析揭示了该 Hox 基因在胚胎后发育过程中塑造大脑谱系结构的新的细胞自主作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c763/3507175/3eb475f4516c/bio-01-10-1006-f01.jpg

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