DrosophilaMon1 constitutes a novel node in the brain-gonad axis that is essential for female germline maturation

Abstract

Monensin-sensitive 1 (Mon1) is an endocytic regulator that participates in the conversion of Rab5-positive early endosomes to Rab7-positive late endosomes. In Drosophila, loss of mon1 leads to sterility as the mon1 mutant females have extremely small ovaries with complete absence of late stage egg chambersa phenotype reminiscent of mutations in the insulin pathway genes. Here, we show that expression of many Drosophila insulin-like peptides (ILPs) is reduced in mon1 mutants and feeding mon1 adults an insulin-rich diet can rescue the ovarian defects. Surprisingly, however, mon1 functions in the tyramine/ octopaminergic neurons (OPNs) and not in the ovaries or the insulinproducing cells (IPCs). Consistently, knockdown of mon1 in only the OPNs is sufficient to mimic the ovarian phenotype, while expression of the gene in the OPNs alone can 'rescue' the mutant defect. Last, we have identified ilp3 and ilp5 as critical targets of mon1. This study thus identifies mon1 as a novel molecular player in the brain-gonad axis and underscores the significance of inter-organ systemic communication during development.

Monensin Sensitive 1 Regulates Dendritic Arborization in Drosophila by Modulating Endocytic Flux

“…Mon1 may thus regulate anterograde signaling in synapses, both neuron:neuron or neuron:muscle. Recent research from our laboratory (Dhiman et al, 2019) also suggests that Mon1 in Octopaminergic neurons regulates systemic insulin signaling by regulating insulin producing cells.…”

“…In this study we demonstrate that Drosophila Monensin Sensitivity 1 (DMon1; Yousefian et al, 2013; Deivasigamani et al, 2015; Dhiman et al, 2019), a core component of the Mon1:CCZ1 complex (Wang et al, 2002; Nordmann et al, 2010; Poteryaev et al, 2010), and central to conversion of early endosomes to late endosomes, regulates morphogenesis of Class IV da (CIVda) neurons. We uncover a role for Mon1 by demonstrating that CIVda patterning can be regulated by increasing or decreasing Mon1 function during embryonic/larval development: loss of Mon1 leads to increased branching while overexpression suppresses it.…”

Redundant functions of the SLC5A transporters Rumpel, Bumpel, and Kumpel in ensheathing glial cells

“…For example, the neurotransmitter octopamine, which is closely related to norepinephrine, is known to act as an alerting signal in insects and octopaminergic neurons reach almost all peripheral tissues ( Pauls et al, 2018 ). The endocytic regulator monensin-sensitive 1 (Mon1) is required in octopaminergic neurons for normal ovary growth and a cell-type specific knockdown results in the absence of late-stage egg chambers ( Dhiman et al, 2019 ). Octopamine also reaches the insulin producing cells (IPCs), which are known to regulate feeding behavior and express the octopamine receptor OAMB1 ( Luo et al, 2014 ; Selcho and Pauls, 2019 ).…”

Conserved neuropeptidergic regulation of intestinal integrity in invertebrate models of aging

“…Decline in germline function and reproductive capacity is one of the early aging phenotypes 72 . Nematode DAF-28 and fly Dilp3 are both required for proper germline maturation during development 58,73 , however these peptides become undetectable in post-reproductive adult nematodes and, flies 74 . Collectively, these data suggest an intriguing hypothesis – that germline activity modifies neuronal signaling, which in turn impacts intestinal aging.…”