Midgut-derived neuropeptide F controls germline stem cell proliferation in a mating-dependent manner

Abstract

Stem cell maintenance is established by neighboring niche cells that promote stem cell self-renewal. However, it is poorly understood how stem cell activity is regulated by systemic, tissue-extrinsic signals in response to environmental cues and changes in physiological status. Here, we show that neuropeptide F (NPF) signaling plays an important role in the pathway regulating mating-induced germline stem cell (GSC) proliferation in the fruit fly Drosophila melanogaster. NPF expressed in enteroendocrine cells (EECs) of the midgut is released in response to the seminal-fluid protein sex peptide (SP) upon mating. This midgut-derived NPF controls mating-induced GSC proliferation via ovarian NPF receptor (NPFR) activity, which modulates bone morphogenetic protein (BMP) signaling levels in GSCs. Our study provides a molecular mechanism that describes how a gut-derived systemic factor couples stem cell behavior to physiological status, such as mating, through interorgan communication.

The Cellular Diversity and Transcription Factor Code of Drosophila Enteroendocrine Cells

“…Communication between EEs and enterocytes via Tk signaling has also been implicated in controlling lipid metabolism in enterocytes . It has been recently reported that the gut-derived NPF could also impact on the proliferation of germline stem cells in the ovary (Ameku et al, 2018). It may worth mentioning that EEs could also be signal-receiving cells from signals produced by other organs.…”

“…The EEs are scattered along the epithelium of the entire midgut, including anterior midgut (regions R1 and R2), middle midgut (the gastric region, R3) and posterior midgut (regions R4 and R5) (Buchon et al, 2013;Marianes and Spradling, 2013). They have important roles in regulating local stem cell division and lipid metabolism, as well as feeding and mating behaviors (Amcheslavsky et al, 2014;Ameku et al, 2018;Min et al, 2016;Song et al, 2014). Approximately 10 peptide hormone genes are found to be expressed in EEs, yielding more than 20 different peptide hormones (Reiher et al, 2011;Veenstra and Ida, 2014;Veenstra et al, 2008).…”

The multifaceted role of nerves in animal regeneration

“…Neuropeptide F (NPF) stimulates mitotic activity of neoblasts and promotes pharyngeal regeneration in planarians [87]. Interestingly, a pro-mitogenic action of NPF was recently shown in the germ stem cells niche of Drosophila [88]. Hydra polyps regeneration depends on the Head Activator (HA) neuro-peptide, which promotes proliferation and differentiation of nerve and epithelial cells, via the cAMP pathway [58,89].…”

Neuropeptide F receptor acts in theDrosophilaprothoracic gland to regulate growth and developmental timing

“…1B, p = 0.01). Therefore, to further verify that NPFR regulates developmental timing, we tested an NPFR loss of function mutant strain (NPFR SK8 ; [23]). The NPFR SK8 mutant larvae also displayed a significant delay in time to pupariation compared to a heterozygous control (~15 hours; Fig.…”

“…Either a local or systemic source of NPF is therefore possible for activating NPFR in the PG. While neuropeptides such as NPF are best described as having local modes of action, in the adult fly NPF has recently been shown to be secreted from the midgut into the hemolymph, where it can act systemically [23]. In the larva NPF is known to be expressed in dopaminergic neurons in the brain, as well as cells in the midgut [20].…”