Drosophila septin interacting protein 1 regulates neurogenesis in the early developing larval brain

Jia-Yi Wei,Sao-Yu Chu,Pei-Chi Chung,Hung-Hsiang Yu,Yu-Chien Huang

doi:10.1038/s41598-021-04474-3

Jia-Yi Wei, Sao-Yu Chu + Show 3 more

Open Access

https://doi.org/10.1038/s41598-021-04474-3

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Abstract

Neurogenesis in the Drosophila central brain progresses dynamically in order to generate appropriate numbers of neurons during different stages of development. Thus, a central challenge in neurobiology is to reveal the molecular and genetic mechanisms of neurogenesis timing. Here, we found that neurogenesis is significantly impaired when a novel mutation, Nuwa, is induced at early but not late larval stages. Intriguingly, when the Nuwa mutation is induced in neuroblasts of olfactory projection neurons (PNs) at the embryonic stage, embryonic-born PNs are generated, but larval-born PNs of the same origin fail to be produced. Through molecular characterization and transgenic rescue experiments, we determined that Nuwa is a loss-of-function mutation in Drosophila septin interacting protein 1 (sip1). Furthermore, we found that SIP1 expression is enriched in neuroblasts, and RNAi knockdown of sip1 using a neuroblast driver results in formation of small and aberrant brains. Finally, full-length SIP1 protein and truncated SIP1 proteins lacking either the N- or C-terminus display different subcellular localization patterns, and only full-length SIP1 can rescue the Nuwa-associated neurogenesis defect. Taken together, these results suggest that SIP1 acts as a crucial factor for specific neurogenesis programs in the early developing larval brain.

Highlights

Neurogenesis in the Drosophila central brain progresses dynamically in order to generate appropriate numbers of neurons during different stages of development
We found that the number of ventral olfactory projection neurons (vPNs) was drastically reduced in the homozygous mutation caused by a P-element insertion line (Kyoto Drosophila Genome Research Center/DGRC 111,477, referred to as P111477) when MARCM neuroblast clones were induced at NHL-24 h ALH (4.2 ± 1.3, n = 14, P < 0.01; Fig. 1c,h; Supplemental Fig. 1)
To investigate whether the P111477 mutation generally impairs the production of vPNs, we examined the vPN number in MARCM neuroblast clones induced at later developmental stages

Summary

Introduction

Neurogenesis in the Drosophila central brain progresses dynamically in order to generate appropriate numbers of neurons during different stages of development. Full-length SIP1 protein and truncated SIP1 proteins lacking either the N- or C-terminus display different subcellular localization patterns, and only full-length SIP1 can rescue the Nuwa-associated neurogenesis defect Taken together, these results suggest that SIP1 acts as a crucial factor for specific neurogenesis programs in the early developing larval brain. In our ongoing MARCM (mosaic analysis with a repressible cell marker)12-based genetic screen for modulators of neurogenesis, we identified a novel mutation, Nuwa In this mutant line, we found impaired neurogenesis in all examined neural lineages when the homozygous mutation was induced at the early larval but not embryonic or late larval stages. We found that full-length SIP1 protein and truncated SIP1 proteins displayed preferential subcellular localizations, and only full-length SIP1 protein could rescue the Nuwa-associated neurogenesis defects Taken together, these results suggest that SIP1 acts as a crucial factor for neurogenesis processes in the early developing larval brain

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