Adult‐specific insulin‐producing neurons in Drosophila melanogaster

Abstract

Holometabolous insects undergo metamorphosis to reorganize their behavioral and morphological features into adult-specific ones. In the central nervous system (CNS), some larval neurons undergo programmed cell death, whereas others go through remodeling of axonal and dendritic arbors to support functions of re-established adult organs. Although there are multiple neuropeptides that have stage-specific roles in holometabolous insects, the reorganization pattern of the entire neuropeptidergic system through metamorphosis still remains largely unclear. In this study, we conducted a mapping and lineage tracing of peptidergic neurons in the larval and adult CNS by using Drosophila genetic tools. We found that Diuretic hormone 44-producing median neurosecretory cells start expressing Insulin-like peptide 2 in the pharate adult stage. This neuronal cluster projects to the corpora cardiaca and dorsal vessel in both larval and adult stages, and also innervates an adult-specific structure in the digestive tract, the crop. We propose that the adult-specific insulin-producing cells may regulate functions of the digestive system in a stage-specific manner. Our study provides a neuroanatomical basis for understanding remodeling of the neuropeptidergic system during insect development and evolution.

Recent advances in neuropeptide signaling in Drosophila, from genes to physiology and behavior

“…DILP1 can normally be found only during the pupal stage and first few days of adult life, whereas the others are produced throughout larval-adult stages [274]. Recently it was found that in adult flies DILP2 is produced in six additional neurosecretory cells adjacent to the IPCs, the DH44-producing MNCs [275]. DILP6 is produced by the adipocytes of the fat body, and is especially abundant during pupal development [156,530].…”

“…The anterior four out of these eleven pairs coexpress DH44 [150]. DH44, in addition, is expressed in three pairs of median neurosecretory cells in the brain [543], which in adults co-express DILP2 [275]. Capa peptides are solely expressed in three pairs of neurosecretory cells in the abdominal ganglia A2-A4 [132,653].…”

Molecular and circuit mechanisms mediating circadian clock output in the Drosophila brain

“…Three different PI groups, those that express DH44 (Diuretic hormone 44), SIFa (SIFamide) or DILP2 ( Drosophila insulin‐like peptide 2), synapse with DN1p clock neurons (Barber, Erion, Holmes, & Sehgal, ; Cavanaugh et al., ). The three PI groups are largely distinct from one another, with the exception that a pair of the Dh44 + neurons expresses low levels of DILP2 (Ohhara, Kobayashi, Yamakawa‐Kobayashi, & Yamanaka, ). Currently, it is not known whether s‐LNvs or other clock neurons directly signal to the PI.…”

DH44 neurons: gut-brain amino acid sensors

“…Interestingly, of the six DH44 neurons in the adult, some were found to co-express Drosophila insulin-like peptide 2 (Dilp2), a known regulator for energy metabolism and growth, and these adult-specific IPCs/ DH44 neurons innervate the crop. 9 It will be of interest to determine whether Dilp2 expression maps to amino acid-sensing DH44 neurons, positing that as one mechanism by which Dilp release can be regulated under different physiological conditions. Lastly, there is an intriguing possibility of other amino acidsensing neurons in the pars intercerebralis (PI) region, given that additional neurons juxtaposed with the six DH44 neurons express the putative amino acid transporter, CG13248.…”

“…How do DH44-R1 neurons in the central nervous system 8 act together with DH44-R2 enteroendocrine cells in the gut 8 to regulate consumption? Since the six DH44 neurons are preserved through metamorphosis, 9 do these sensors also function in larvae? What behaviors or physiological processes rely on the small increase in food intake occurring over seconds that is controlled by DH44 signaling?…”