scholarly journals Shaping the size of a neuronal lineage: the role of Imp and Syp RBPs in the precise elimination of neurons by apoptosis.

2021 ◽  
Author(s):  
Jonathan ENRIQUEZ ◽  
Wenyue GUAN ◽  
Mathilde BOUCHET ◽  
Aurelien DARMAS

Neuronal stem cells produce a finite and stereotyped number of neuronal progenies. This process must be finely regulated during development and adult stages to ensure proper brain function. In Drosophila, stem cells, called Neuroblasts, produce an invariant number of neurons. Two RNA binding proteins, Imp and Syp, play a central role in controlling the speed of division and the end of the proliferative phase of individual NBs, two parameters that influences the final number of neurons produced. Here, we have discovered a novel function for Imp and Syp, where both RBPs shape the number of neurons produced by a stem cell by controlling program cell death (PCD) in immature neurons. By studying a neuroblast lineage, called Lin A/15, which produces motoneurons (MNs) and glia, we have demonstrated that Lin A/15 stem cell spends 40% of its time producing immature MNs which are eliminated by apoptosis. We have revealed that only the first born MNs (Imp +) survive while the last born MNs (Imp- Syp+) are eliminated by apoptosis. Both RBPs play a central role in neuronal survival, Imp promotes neuronal survival while Syp promotes cell death in immature motoneurons. Interestingly their opposite temporal gradient in Lin A/15 stem cell also determines the end of Lin A/15 stem cell neurogenesis by PCD. Both RNA binding proteins are conserved in vertebrates and seem to play a central role in the number of neurons produce during development. The Drosophila model and its genetic tools offer a unique chance to decipher their function in neural stem cell versus immature neurons.

2018 ◽  
Author(s):  
Douglas F. Porter ◽  
Aman Prasad ◽  
Brian H. Carrick ◽  
Peggy Kroll-Connor ◽  
Marvin Wickens ◽  
...  

AbstractMetazoan PUF (Pumilio and FBF) RNA-binding proteins regulate various biological processes, but a common theme across phylogeny is stem cell regulation. In Caenorhabditis elegans, FBF (fem-3 Binding Factor) maintains germline stem cells regardless of which gamete is made, but FBF also functions in the process of spermatogenesis. We have begun to “disentangle” these biological roles by asking which FBF targets are gamete-independent, as expected for stem cells, and which are gamete-specific. Specifically, we compared FBF iCLIP binding profiles in adults making sperm to those making oocytes. Normally, XX adults make oocytes. To generate XX adults making sperm, we used a fem-3(gf) mutant requiring growth at 25°; for comparison, wild-type oogenic hermaphrodites were also raised at 25°. Our FBF iCLIP data revealed FBF binding sites in 1522 RNAs from oogenic adults and 1704 RNAs from spermatogenic adults. More than half of these FBF targets were independent of germline gender. We next clustered RNAs by FBF-RNA complex frequencies and found four distinct blocks. Block I RNAs were enriched in spermatogenic germlines, and included validated target fog-3, while Block II and III RNAs were common to both genders, and Block IV RNAs were enriched in oogenic germlines. Block II (510 RNAs) included almost all validated FBF targets and was enriched for cell cycle regulators. Block III (21 RNAs) was enriched for RNA-binding proteins, including previously validated FBF targets gld-1 and htp-1. We suggest that Block I RNAs belong to the FBF network for spermatogenesis, and that Blocks II and III are associated with stem cell functions.


Development ◽  
2017 ◽  
Vol 144 (19) ◽  
pp. 3454-3464 ◽  
Author(s):  
Ching-Po Yang ◽  
Tamsin J. Samuels ◽  
Yaling Huang ◽  
Lu Yang ◽  
David Ish-Horowicz ◽  
...  

PLoS Genetics ◽  
2014 ◽  
Vol 10 (11) ◽  
pp. e1004797 ◽  
Author(s):  
Di Chen ◽  
Chan Wu ◽  
Shaowei Zhao ◽  
Qing Geng ◽  
Yu Gao ◽  
...  

2019 ◽  
Vol 97 (1) ◽  
pp. 10-20 ◽  
Author(s):  
Laura P.M.H. de Rooij ◽  
Derek C.H. Chan ◽  
Ava Keyvani Chahi ◽  
Kristin J. Hope

Normal hematopoiesis is sustained through a carefully orchestrated balance between hematopoietic stem cell (HSC) self-renewal and differentiation. The functional importance of this axis is underscored by the severity of disease phenotypes initiated by abnormal HSC function, including myelodysplastic syndromes and hematopoietic malignancies. Major advances in the understanding of transcriptional regulation of primitive hematopoietic cells have been achieved; however, the post-transcriptional regulatory layer that may impinge on their behavior remains underexplored by comparison. Key players at this level include RNA-binding proteins (RBPs), which execute precise and highly coordinated control of gene expression through modulation of RNA properties that include its splicing, polyadenylation, localization, degradation, or translation. With the recent identification of RBPs having essential roles in regulating proliferation and cell fate decisions in other systems, there has been an increasing appreciation of the importance of post-transcriptional control at the stem cell level. Here we discuss our current understanding of RBP-driven post-transcriptional regulation in HSCs, its implications for normal, perturbed, and malignant hematopoiesis, and the most recent technological innovations aimed at RBP–RNA network characterization at the systems level. Emerging evidence highlights RBP-driven control as an underappreciated feature of primitive hematopoiesis, the greater understanding of which has important clinical implications.


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