The role of Imp and Syp RNA-binding proteins in precise neuronal elimination by apoptosis through the regulation of transcription factors

• Published in: eLife Vol. 12
• Main Authors: Guan, Wenyue, Nie, Ziyan, Laurençon, Anne, Bouchet, Mathilde, Godin, Christophe, Kabir, Chérif, Darnas, Aurelien, Enriquez, Jonathan
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 04.10.2024; eLife Sciences Publications Ltd
• Subjects: Abdomen; Animals; Apoptosis; Autophagy; Cell death; Cell survival; Drosophila - metabolism; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Gene expression; Gene Expression Regulation, Developmental; Gene regulation; Genetic aspects; Insects; Kinases; motoneuron; Motor neurons; Motor Neurons - metabolism; Nervous system; Neural stem cells; Neural Stem Cells - metabolism; Neurogenesis; Neurological research; Neuronal-glial interactions; Neurons; Neurons - metabolism; Physiological aspects; programmed cell death; Proteins; RNA-binding protein; RNA-binding proteins; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Stem cells; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; France; transcription factors; developmental biology; motoneuron; neurogenesis; RNA-binding proteins; D. melanogaster; programmed cell death
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.91634

Neuronal stem cells generate a limited and consistent number of neuronal progenies, each possessing distinct morphologies and functions, which are crucial for optimal brain function. Our study focused on a neuroblast (NB) lineage in Drosophila known as Lin A/15, which generates motoneurons (MNs) and glia. Intriguingly, Lin A/15 NB dedicates 40% of its time to producing immature MNs (iMNs) that are subsequently eliminated through apoptosis. Two RNA-binding proteins, Imp and Syp, play crucial roles in this process. Imp+ MNs survive, while Imp−, Syp+ MNs undergo apoptosis. Genetic experiments show that Imp promotes survival, whereas Syp promotes cell death in iMNs. Late-born MNs, which fail to express a functional code of transcription factors (mTFs) that control their morphological fate, are subject to elimination. Manipulating the expression of Imp and Syp in Lin A/15 NB and progeny leads to a shift of TF code in late-born MNs toward that of early-born MNs, and their survival. Additionally, introducing the TF code of early-born MNs into late-born MNs also promoted their survival. These findings demonstrate that the differential expression of Imp and Syp in iMNs links precise neuronal generation and distinct identities through the regulation of mTFs. Both Imp and Syp are conserved in vertebrates, suggesting that they play a fundamental role in precise neurogenesis across species.