Post-Transcriptional Regulation of Transcription Factor Codes in Immature Neurons Drives Neuronal Diversity
37 Pages Posted: 7 Mar 2022 Publication Status: PublishedMore...
How the vast array of neuronal diversity is generated remains an unsolved problem. Here, we investigated how 29 morphologically distinct leg motoneurons are generated from a single stem cell in Drosophila. We identified 19 transcription factor (TF) codes expressed in immature motoneurons just before their morphological differentiation. We demonstrated with the help of genetic manipulations and a novel computational tool that the TFs codes are progressively established in iMNs as a function of their birth order. Comparison of RNA and protein expression patterns of multiple TFs revealed that post-transcriptional regulation plays an essential role in shaping these TF codes. We showed for the first time that two RNA binding proteins, Imp and Syp, are expressed in opposite gradients in immature post-mitotic motoneurons and control the translation of multiple TFs. The varying sensitivity of TF mRNAs to the opposite gradients of Imp and Syp in immature motoneurons decrypts these gradients into distinct TF codes, which in turn establish the connectome between motoneuron axons and their target muscles.
Keywords: Neuronal diversity, Transcription Factor (TF) codes, post-transcriptional regulation, RNA binding proteins, Immature post-mitotic motoneurons
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