The transcription elongation factors Spt4 and Spt5 control neural progenitor proliferation and are implicated in neuronal remodeling during Drosophila mushroom body development.

IF 4.6 2区 生物学 Q2 CELL BIOLOGY
Frontiers in Cell and Developmental Biology Pub Date : 2024-10-09 eCollection Date: 2024-01-01 DOI:10.3389/fcell.2024.1434168
Lea Barthel, Stefani Pettemeridi, Ali Nebras, Hayley Schnaidt, Karoline Fahland, Lea Vormwald, Thomas Raabe
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Abstract

Spt4 and Spt5 form the DRB sensitivity inducing factor (DSIF) complex that regulates transcription elongation at multiple steps including promotor-proximal pausing, processivity and termination. Although this implicated a general role in transcription, several studies pointed to smaller sets of target genes and indicated a more specific requirement in certain cellular contexts. To unravel common or distinct functions of Spt4 and Spt5 in vivo, we generated knock-out alleles for both genes in Drosophila melanogaster. Using the development of the mushroom bodies as a model, we provided evidence for two common functions of Spt4 and Spt5 during mushroom body development, namely control of cell proliferation of neural progenitor cells and remodeling of axonal projections of certain mushroom body neurons. This latter function is not due to a general requirement of Spt4 and Spt5 for axon pathfinding of mushroom body neurons, but due to distinct effects on the expression of genes controlling remodeling.

转录延伸因子Spt4和Spt5控制神经祖细胞的增殖,并与果蝇蘑菇体发育过程中的神经元重塑有关。
Spt4 和 Spt5 组成了 DRB 敏感性诱导因子(DSIF)复合物,在多个步骤上调节转录延伸,包括启动子近端暂停、过程性和终止。尽管这暗示了DRB在转录中的一般作用,但一些研究指出了较小的目标基因集,并指出了在某些细胞环境中更特殊的要求。为了揭示 Spt4 和 Spt5 在体内的共同或不同功能,我们在黑腹果蝇中产生了敲除这两个基因的等位基因。我们以蘑菇体的发育为模型,证明了Spt4和Spt5在蘑菇体发育过程中的两种共同功能,即控制神经祖细胞的细胞增殖和重塑某些蘑菇体神经元的轴突突起。后一种功能并不是因为蘑菇体神经元的轴突寻路普遍需要Spt4和Spt5,而是因为它们对控制重塑的基因的表达有不同的影响。
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来源期刊
Frontiers in Cell and Developmental Biology
Frontiers in Cell and Developmental Biology Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
9.70
自引率
3.60%
发文量
2531
审稿时长
12 weeks
期刊介绍: Frontiers in Cell and Developmental Biology is a broad-scope, interdisciplinary open-access journal, focusing on the fundamental processes of life, led by Prof Amanda Fisher and supported by a geographically diverse, high-quality editorial board. The journal welcomes submissions on a wide spectrum of cell and developmental biology, covering intracellular and extracellular dynamics, with sections focusing on signaling, adhesion, migration, cell death and survival and membrane trafficking. Additionally, the journal offers sections dedicated to the cutting edge of fundamental and translational research in molecular medicine and stem cell biology. With a collaborative, rigorous and transparent peer-review, the journal produces the highest scientific quality in both fundamental and applied research, and advanced article level metrics measure the real-time impact and influence of each publication.
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