Abstract
ABSTRACTDuring Drosophila and vertebrate brain development, the conserved transcription factor Prospero/Prox1 is an important regulator of the transition between proliferation and differentiation. Prospero level is low in neural stem cells and their immediate progeny, but is upregulated in larval neurons and it is unknown how this process is controlled. Here, we use single molecule fluorescent in situ hybridisation to show that larval neurons selectively transcribe a long prospero mRNA isoform containing a 15 kb 3′ untranslated region, which is bound in the brain by the conserved RNA-binding protein Syncrip/hnRNPQ. Syncrip binding increases the stability of the long prospero mRNA isoform, which allows an upregulation of Prospero protein production. Adult flies selectively lacking the long prospero isoform show abnormal behaviour that could result from impaired locomotor or neurological activity. Our findings highlight a regulatory strategy involving alternative polyadenylation followed by differential post-transcriptional regulation.This article has an associated First Person interview with the first author of the paper.
Highlights
The central nervous system (CNS) consists of a huge diversity and number of neurons that originate from a limited population of neural stem cells (NSCs) (Kelava and Lancaster, 2016), known as neuroblasts (NBs) in Drosophila
Upregulation of Pros protein in neurons is achieved through cell type-specific stabilisation of pros mRNA Pros protein is expressed at low levels in larval type I NBs and GMCs, where it promotes GMC differentiation, and is upregulated in larval neurons (Carney et al, 2013; Choksi et al, 2006)
As previously shown (Carney et al, 2013; Choksi et al, 2006), we found that Pros expression is low in NBs and GMCs and is upregulated in Elav+, post-mitotic neurons (Fig. 1B). pros exon single molecule fluorescent in situ hybridisation (smFISH) signal is upregulated in Elav+ cells, and correlates with the increased Pros protein expression (Fig. 1B)
Summary
The central nervous system (CNS) consists of a huge diversity and number of neurons that originate from a limited population of neural stem cells (NSCs) (Kelava and Lancaster, 2016), known as neuroblasts (NBs) in Drosophila. To produce a normal CNS, NBs must divide the correct number of times and their progeny must undergo a precisely regulated programme of differentiation. Many factors and mechanisms regulating these processes have been studied in detail, and are extensively conserved between vertebrates and Drosophila (Homem and Knoblich, 2012). The emphasis in the field has been on identifying key transcription factors and their downstream transcriptional effects. Received 27 November 2019; Accepted 24 February 2020 regulation, which can modulate protein expression with enhanced spatial and temporal precision, has been less well characterised
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