The Insulin Receptor Is Required for the Development of the Drosophila Peripheral Nervous System

Abstract

The Insulin Receptor (InR) in Drosophila presents features conserved in its mammalian counterparts. InR is required for growth; it is expressed in the central and embryonic nervous system and modulates the time of differentiation of the eye photoreceptor without altering cell fate. We show that the InR is required for the formation of the peripheral nervous system during larval development and more particularly for the formation of sensory organ precursors (SOPs) on the fly notum and scutellum. SOPs arise in the proneural cluster that expresses high levels of the proneural proteins Achaete (Ac) and Scute (Sc). The other cells will become epidermis due to lateral inhibition induced by the Notch (N) receptor signal that prevents its neighbors from adopting a neural fate. In addition, misexpression of the InR or of other components of the pathway (PTEN, Akt, FOXO) induces the development of an abnormal number of macrochaetes that are Drosophila mechanoreceptors. Our data suggest that InR regulates the neural genes ac, sc and sens. The FOXO transcription factor which is localized in the cytoplasm upon insulin uptake, displays strong genetic interaction with the InR and is involved in Ac regulation. The genetic interactions between the epidermal growth factor receptor (EGFR), Ras and InR/FOXO suggest that these proteins cooperate to induce neural gene expression. Moreover, InR/FOXO is probably involved in the lateral inhibition process, since genetic interactions with N are highly significant. These results show that the InR can alter cell fate, independently of its function in cell growth and proliferation.

Regulation of cuticle pigmentation in drosophila by the nutrient sensing insulin and TOR signaling pathways

“…). This finding is consistent with a recent study that found that loss of Insulin signaling in proneural clusters results in decreased bristle production on the thorax (Dutriaux et al, ). Despite the changes seen in bristle morphology and density, we did not see an effect of Insulin signaling on bristle pigmentation.…”

Insulin Receptor–Mediated Signaling Regulates Pluripotency Markers and Lineage Differentiation

“…IRKO iPSCs showed an upregulation of neuronal markers including early neural progenitor markers such as Pax6, Tubb3, Oligo2 and Ascl1. This is consistent with the report that the insulin receptor is involved in development of the peripheral nervous system in drosophila [42]. On the contrary, adipocytes differentiated from IRKO iPSCs presented features of reduced adipogenesis.…”

Convergent evolution associated with the loss of developmental diapause may promote extended lifespan in bees

“…The box in the bottom right classifies the genes as pro– or anti-longevity based on their known effects on Drosophila lifespan (Tacutu et al 2018). Figure made based on Kapahi and Zid 2004; Dutriaux et al 2013; Texada et al 2020; Denlinger 2022.…”

“…During diapause, the brain-PG axis is shut down, inhibiting PTTH production and release, subsequently reducing production of ecdysteroids, resulting in delayed metamorphosis (Fig. 4) (Denlinger 2022).…”