1. The post-transcriptional regulation of TFs in immature motoneurons shapes the axon-muscle connectome
- Author
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Mathilde Bouchet, Jonathan Enriquez, Stéphanie Bellemin, Camille Guillermin, Séverine Urdy, Christophe Godin, Anne Laurençon, Richard S. Mann, Kabir Chérif, Aurélien Darmas, Lalanti Venkatasubramanian, Wenyue Guan, Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Columbia University [New York], Centre National de la Recherche Scientifique (CNRS), Enriquez, Jonathan, and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
- Subjects
0303 health sciences ,Messenger RNA ,[SDV]Life Sciences [q-bio] ,RNA ,RNA-binding protein ,Biology ,Neural stem cell ,Cell biology ,[SDV] Life Sciences [q-bio] ,03 medical and health sciences ,0302 clinical medicine ,Stem cell ,Transcription factor ,Post-transcriptional regulation ,030217 neurology & neurosurgery ,Function (biology) ,030304 developmental biology - Abstract
SUMMARYTemporal factors expressed sequentially in neural stem cells, such as RNA binding proteins (RBPs) or transcription factors (TFs), are key elements in the generation of neuronal diversity. The molecular mechanism underlying how the temporal identity of stem cells is decoded into their progeny to generate neuronal diversity is largely unknown. Here, we used genetic and new computational tools to study with precision the unique fates of the progeny of a stem cell producing 29 morphologically distinct leg motoneurons (MNs) in Drosophila. We identified 40 TFs expressed in this MN lineage, 15 of which are expressed in a combinatorial manner in immature MNs just before their morphological differentiation. By following TF expression patterns at an earlier developmental stages, we discovered 19 combinatorial codes of TFs that were progressively established in immature MNs as a function of their birth order. The comparison of the RNA and protein expression profiles of 6 TFs revealed that post-transcriptional regulation plays an essential role in shaping these TF codes. We found that the two known RBPs, Imp and Syp, expressed sequentially in neuronal stem cells, are upstream regulators of the TF codes. Both RBPs are key players in the construction of axon-muscle connectome through the post-transcriptional regulation of 5 of the 6 TFs examined. By deciphering the function of Imp in the immature MNs with respect to the stem cell of the same lineage, we propose a model where RBPs shape the morphological fates of MNs through post-transcriptional regulation of TF codes in immature MNs. Taken together, our study reveals that immature MNs are plastic cells that have the potential to acquire many morphological fates. The molecular basis of MN plasticity originates in the broad expression of different TF mRNA, that are post-transcriptionally shaped into TF codes by Imp and Syp, and potentially by other RBPs that remain to be discovered, to determine their morphological fates.
- Published
- 2021