Based on the connectivity map of hug neurons and the alteration in hug expression under different nutrient and feeding conditions, a series of experiments was initiated to explore the role of hug in regulating feeding. Since hug mutants have not yet been identified, the effects of overexpressing hug in the larvae was tested. hugS3 was used to drive hug expression but no phenotype was observed. This is most likely because using an endogenous promoter does not result in high enough overexpression of hug in cells that already express physiological levels of hug. Therefore a strong ubiquitous promoter (tubulin-gal4) was used. There was a strong reduction in growth, with no larvae surviving to pupal stage; defects in food intake were observed, although not to the same strong degree as with klu mutants. This is consistent with the view that high hug levels correlate with decreased food intake (Melcher, 2005).
In order to gain further information on the function of hug neurons, synaptic transmission in these cells was blocked using tetanus toxin light chain (TeTxLC). The experiments were carried in the larvae but no difference was seen. However, it was reasoned that any potential increase in feeding response may not be readily detectable in the larvae because they feed continuously, already at a maximal rate. Therefore, whether blocking synaptic transmission of hug neurons could suppress the feeding defect of klu mutants was tested. A significant rescue was observed of klu mutant feeding phenotype (Melcher, 2005).
Behavioral analysis on adults was carried out, since they are discontinuous feeders and thus may display an increased feeding behavior. Furthermore, one can visualize the quantity of food eaten by the size of the crop. Experimental and control flies were placed in food vials containing standard fly food for several days. They were then transferred to yeast paste containing red dye. A striking result was observed. After 5 min, the experimental flies had a completely filled crop, whereas the control lines had very little food in the crop. Even after 30 min, the control flies had very little food in their crops and only traces of red food were detectable in the midgut. By 180 min, both experimental and control flies showed the same degree of feeding. These results suggested that hug neurons are involved in regulating the initiation phase of feeding: control flies wait for a certain period before initiating feeding on the new food source, whereas decreasing hug neuronal signaling results in flies initiating their feeding immediately. When flies were transferred from yeast to colored yeast, or normal food to colored normal food, no difference was seen between experimental and control flies, indicating that hug neurons are not simply affecting the rate of feeding per se; no a difference was observed when transferring from yeast to normal food, indicating that the hug neuron-dependent behavioral effect is also not due to a simple fact of changing food sources. When flies were transferred from normal food into yeast containing 1M quinine (quinine is an aversive tastant), experimental flies again filled their crops earlier than controls. However, when flies were kept on yeast containing 1M quinine, and then transferred to yeast without the quinine, both experimental and control flies filled their crops with the new yeast within 5 min; analogously, when flies were starved before placing them on red yeast, both control and experimental flies filled their crops at about the same rate. These results suggest that the quality of previous food condition plays a role in defining hug neuronal function. Taken together, these studies support the view that hug neurons act within a neural circuitry in the brain that modulates feeding behavior based on chemosensory and nutrient signals (Melcher, 2005).
Both putative peptides encoded by the hugin gene, Drm-PK-2 and hugγ, were consecutively tested on the same hyperneural muscle preparations. Threshold values for myostimulatory effects of the peptides differed clearly. The hugγ peptide exhibited a very low potency; Drm-PK-2 had a threshold concentration of about 3×10−8 M, thus being slightly less active than the sequence-related pyrokinin Pea-PK-3. The response of Drosophila heart preparations to Drm-PK-2 was a moderate increase in frequency not exceeding 150% of the control, even if the concentration was as high as 10−6 M (threshold at about 10−9 M). In contrast, most preparations showed a clear increase in amplitude after pyrokinin application with a threshold as low as. These results show that Drm-PK-2 has pyrokinin activity (Meng, 2002).
Two groups of GPCRs have been characterized predicted as receptors for peptides with a C-terminal amino acid sequence motif consisting of -PRXamide (PRXa). The insect PRXa peptides are evolutionarily related to the vertebrate peptide neuromedin U (NMU), or are related to arginine vasopressin (AVP), both of which have PRXa motifs. Seven Drosophila GPCRs related to receptors for NMU and AVP were cloned and expressed in Xenopus oocytes for functional analysis. Four Drosophila GPCRs in the NMU group (CG14575, CG8795, CG9918, CG8784) are activated by insect PRXa pyrokinins, (-FXPRXamide), Cap2b-like peptides (-FPRXamide), or ecdysis triggering hormones (-PRXamide). Three Drosophila GPCRs in the vasopressin receptor group respond to crustacean cardioactive peptide (CCAP), corazonin, or adipokinetic hormone (AKH), none of which are PRXa peptides. These findings support a theory of coevolution for NMU and Drosophila PRXa peptides and their respective receptors (Park, 2002).
The database of the Drosophila Genome Project contains the sequences of two genes, CG8784 and CG8795, predicted to code for two structurally related G protein-coupled receptors. These genes have been cloned their coding parts were expressed in Chinese hamster ovary cells. Both receptors can be activated by low concentrations of the Drosophila neuropeptide pyrokinin-2. The precise role of Drosophila pyrokinin-2 (SVPFKPRLamide) in Drosophila is unknown, but in other insects, pyrokinins have diverse myotropic actions and are also initiating sex pheromone biosynthesis and embryonic diapause. Gene silencing, using the RNA-mediated interference technique, showed that CG8784 gene silencing caused lethality in embryos, whereas CG8795 gene silencing resulted in strongly reduced viability for both embryos and first instar larvae. In addition to the two Drosophila receptors, two probable pyrokinin receptors were identified in the genomic database from the malaria mosquito Anopheles gambiae. The two Drosophila pyrokinin receptors are the first invertebrate pyrokinin receptors to be identified (Rosenkilde, 2003).
hug is expressed specifically in a small group of neurons in the SOG. To gain insight into the physiological processes that hug-expressing neurons (referred to as hug neurons) could be involved in, their connectivity pattern was determined. Therefore, a hug promoter-Gal4 line (hugS3) was constructed in order to express different versions of green fluorescent protein (GFP) marker genes for neuroanatomical studies. This approach revealed hug neuron projection to the ring gland. The ring gland, as the master neuroendocrine organ of Drosophila larvae, controls metabolism and growth. For example, median neurosecretory cells of the pars intercerebralis that express Drosophila insulin like peptides (dilps), also project to the ring gland, whereas Adipokinetic hormone (Akh), thought to be a glucagon homolog, is produced by the ring gland (Melcher, 2005).
In addition to the ring gland, hug neuron projection was observed to the protocerebrum, near the median neurosecretory cells and the mushroom bodies, which comprise the center for olfactory learning and memory. The axons projecting to the protocerebrum also cross at the midline just above the foramen. An intriguing glomerular-like structure was observed of what are most likely hug dendrites in the SOG, just dorsoanterior to the hug cell bodies. Glomerular organization in the SOG of adult Drosophila that relays gustatory information has been described. Such a glomerular organization has not been previously recognized for the larval SOG, but it would be analogous to the glomerular organization in the antennal lobes that relay olfactory information (Melcher, 2005).
Strikingly, there is also projection of hug neurons to the pharyngeal muscles, which pump food into the mouth atrium. These arise from axons that leave the brain and project anteriorly along each side of the dorsal pharyngeal muscles, and terminate near the anterior end of the pharynx. There has been no previous case of identified neurons in the larval SOG that project to motor outputs. At this point, it is not know whether the pharyngeal muscles are actually innervated by these axons. Taken together, these results demonstrate that hug neurons in the larvae project to key organs regulating feeding and growth—namely, the pharynx and the ring gland—as well as to higher brain centers (Melcher, 2005).
The projection of hug neurons to the mushroom body region, together with the fact that hug is expressed specifically in the SOG, which relays gustatory information, suggested that hug neurons could be involved in mediating chemosensory signals. Therefore, whether hug neurons receive direct input from the chemosensory organs was investigated. It has been demonstrated that sensory organs in the larval head that express ORs or GRs send their axons either to the antennal lobe or the SOG. Recently, an enhancer trap line MJ94 was used to label putative chemosensory organs of the internal pharynx (Gendre, 2004). As internal pharyngeal sensory organs are good candidates for transducing gustatory signals, it was asked if these sensory organs terminate at hug dendrites: they indeed terminate in the contact region of hug dendrites (Melcher, 2005).
To further test this, it was asked if chemosensory neurons that express specific GRs also project to hug dendrites. For example, it has been shown that GR66C1-positive neurons project to the SOG, whereas GR21D1-positive neurons project to the antennal lobe. To see if these sensory projections terminate at or near hug neurons, staining of GR66C1- and GR21D1-positive axon terminals was performed with hug in situ hybridization. GR66C1 receptor neurons indeed project to the vicinity of hug-expressing cells. To see if these axons may potentially make synaptic contacts with hug dendrites, a hug promoter–yellow fluorescent protein (YFP) line (in which YFP was placed directly under the hug promoter) was used in combination with GR promoters driving nSyb-GFP, thus allowing simultaneous visualization of GR axon terminals and hug dendrites. GR66C1-positive neurons project to the glomerular-like SOG region contacted by hug dendrites. GR21D1-positive neurons also project near the hug cells, but by contrast to GR66C1-positive neurons, do not contact hug dendrites. Rather, they terminate dorsoanterior to the hug dendrites, where the antennal lobes are located. Taken together, these results suggested that hug neurons may act as second-order interneurons that relay gustatory information (Melcher, 2005).
To further distinguish the relationship between hug neurons and the olfactory or gustatory systems, it was determined whether hug neurons share the same axon tracts to the mushroom bodies as the second-order neurons that relay olfactory sensory input. The dendrites of these olfactory projection neurons underlie the glomerular structure of the antennal lobes and vertically transduce olfactory information for processing to the mushroom bodies. These projections can be visualized by the enhancer trap line GH146. The axon projections of hug neurons are distinct from olfactory projection neurons: hug neurons project to a more dorsomedial region in the protocerebrum than olfactory projection neurons, and they use different axon tracts. These results essentially rule out hug neurons being olfactory projection neurons. Projection neurons transducing gustatory signals to higher brain centers have not yet been identified. In this context, hug neurons could act as gustatory projection neurons that connect gustatory sensory neurons via SOG with the protocerebrum (Melcher, 2005).
A difference was noticed in the projection specificity among the hug neurons. A series of enhancer trap lines have been isolated that label cells projecting their axons to the ring gland, one of which (Okt30) is co-expressed with hug. When the hug promoter-YFP line (to distinguish it from GFP reporter constructs) was used in combination with the Okt30 ring gland enhancer trap line, it was found that a distinct set of hug neurons project to only the ring gland and not to the protocerebrum, the pharynx, or the ventral cord (Melcher, 2005).
Another subpopulation of hug neurons is revealed by using the TH-Gal4 line. This drives reporter gene expression under the promoter of tyrosine hydroxylase (TH), a key enzyme in dopamine synthesis. Specific hug neurons express TH-Gal4 reporter gene, indicating that a subset of hug neurons might be dopaminergic. When TH-Gal4-driven lacZ is used in combination with hug promoter-YFP, it was observed that TH-positive hug neurons project to only the pharynx and not to the protocerebrum, the ring gland, or the VNC. These results indicate that at least three distinct subpopulations of hug neurons exist: those projecting to only the ring gland, those projecting to only the pharyngeal muscles, and those projecting to the protocerebrum and/or the VNC. The distinct target specificity suggests differences in the function of the hug subpopulations. In the honeybee Apis, the subesophageal-calycal tract neurons are located in the SOG, send axons to the protocerebrum, and receive input from the sensory neurons of the proboscis; these neurons are thought to transduce gustatory information. Some of the hug neurons could act similarly to these honeybee neurons. Based on the connectivity map of the hug neurons, it was also of interest to find if the global targeting of these neurons was altered in klu mutant larvae. Therefore, the hug promoter-YFP construct was crossed into klu mutant background. Although it is not possible to rule out subtle local differences, the basic connectivity pattern is retained in the mutants (Melcher, 2005).
To see if hug neurons might also have a function in the adults, the connectivity pattern was determined in adult animals. There are some noticeable morphological differences in the feeding apparatus and neuroendocrine organs between adults and larvae. One is the presence of the crop in the adult but not in the larva. The crop is a food storage organ, and its absence in the larvae most likely reflects a difference in the feeding habits; whereas adults are intermittent feeders, the larvae feed continuously. Another is the relocation of the neuroendocrine organs. The corpora cardiaca/corpora allata (CC/CA) complex, which comprises part of the ring gland in the larvae, is located right above the proventriculus in the adults, at the junction between the gut and the crop. This is in contrast to the larvae, where it is located on top of the brain hemispheres. Monitoring hugS3 expression in adults, axon projections to the protocerebrum, the CC/CA complex, and the ventral cord were observed. A subpopulation of hug neurons may also be dopaminergic, as in the larvae. To further characterize the projections to the protocerebrum, the OK107 enhancer trap Gal4 line was used together with hug promoter-YFP. These stainings indicate that hug axons traverse along the median neurosecretory cells in the pars intercerebralis, and terminate near the mushroom bodies. The precise targets of hug neurons projecting to the protocerebrum remain to be determined. Taken together, despite the morphological differences, the connectivity pattern of hug neurons is remarkably similar between larvae and adults (Melcher, 2005).
The hugin gene of Drosophila encodes a neuropeptide with homology to mammalian neuromedin U. The hugin-expressing neurons are localized exclusively to the subesophageal ganglion of the central nervous system and modulate feeding behavior in response to nutrient signals. These neurons send neurites to the protocerebrum, the ventral nerve cord, the ring gland, and the pharynx and may interact with the gustatory sense organs. In this study, the morphology of the hugin neurons were investigated at a single-cell level by using clonal analysis. Single cells project to only one of the four major targets (see Melcher, 2007 for an illustration of the connectivity of hugin neurous). In addition, the neurites of the different hugin cells overlap in a specific brain region lateral to the foramen of the esophagus, which could be a new site of neuropeptide release for feeding regulation. This study reveals novel complexity in the morphology of individual hugin neurons, which has functional implication for how they coordinate feeding behavior and growth (Bader, 2007).
Each hugin neuron projects to only one of four major targets. Moreover, it this study reveals complexities in neuromorphology that have not been apparent before. Most notably, all hugin neurons arborize in the subesophageal ganglion (SOG) just lateral and ventral to the foramen, an opening in the Drosophila brain where the esophagus passes through. It is likely that this anatomical interface between CNS and gastrointestinal tract represents a local site for neuropeptide release. The single cell analysis additionally revealed close intermingling, precisely in the SOG, between some of the hugin neuronal projection termini and those of neurons mediating taste information from external and internal chemosensory organs. The gustatory receptor neuronal projections arborizing closest to hugin neurons are GR66a positive. Interestingly, this is a receptor that mediates aversive taste: if GR66a-expressing neurons are rendered nonfunctional by genetic manipulations, flies will feed on aversive substances, such as quinine and caffeine, and artificial activation of GR66a taste neurons elicits avoidance behavior to neutral substances (Bader, 2007, and references therein).
The hugin gene is expressed exclusively in 20 neurons in the SOG of the Drosophila larva, where they project to four distinct targets: the protocerebrum, the ventral nerve cord, the ring gland, and the pharynx. To determine the morphology of individual hugin neurons, the flp out technique was used to generate single cells marked with a fluorescent genetic marker. The details of each neurite target are described. Because it is not known at this point whether the different neurites are axons or dendrites, these terms have not been used in the descriptions (Bader, 2007).
Single clones of hugin cells were obtained that show neurites to the ipsilateral protocerebrum. These cells show arborization ventrolateral to the foramen of the esophagus in a region that is innervated by gustatory receptor neurons expressing GR66a. Connections have been observed between the left and the right protocerebrum, and clones were obtained in which neurites branch onto both hemispheres. Although no cells were observed that go only contralaterally, this is not proof of the nonexistence of such cells. Clones in which four cells on one side of the CNS all project to the ipsilateral protocerebrum. If one assumes the same for the other brain hemisphere, this implies that the protocerebrum is innervated by at least eight cells (Bader, 2007).
Single hugin cells also project down the ventral nerve cord. The morphology of these neurons is striking. In addition to a long process travelling down contralaterally along the lateral neuropile border of the ventral cord, there are four shorter fibers projecting up and down just left and right of the midline. The long neurites that extend down the lateral side of the ventral nerve cord branch out at the tip; the precise targets are not known. The two fibers that project in the anterior direction pass along each side of the foramen and end at the medial part of the protocerebrum. It is thus concluded that at least two neurons per hemisphere innervate the ventral cord. There are 20 hugin neurons, of which there are four pharyngeal and four ring gland neurons. It is likely, then, that the number of ventral cord neurons is four and that the number of protocerebral neurons is eight (Bader, 2007).
Single hugin cells projecting to the contralateral side of the ring gland were also observed. In addition, these cells are characterized by an ipsilateral process that stops lateral to the esophageal foramen. The neurite length observed can vary. Fibers are consistently observed projecting to the border of the antennal lobe and the SOG; however, the processes sometimes extend farther dorsally. This may be due to thinning of fibers in the more dorsal regions. In the ring gland, the hugin cells establish dense arborizations on the side ipsilateral to the entering fiber and weaker arborizations after crossing to the other side. Possible target cells in the ring gland are located in the corpora cardiaca (Bader, 2007).
The fourth class of hugin neurons projects to the anterior pharynx, close to the cephalopharyngeal skeleton. The neurites leave the SOG, make a U-turn, and end at the anterior part of the dorsal pharyngeal muscles. Whether the pharyngeal neurons in fact innervate the muscles is not known. Neurites can be seen that cross the midline and those that do not, but, because the pharyngeal neurons are located close to the midline, this distinction is sometimes difficult. In addition, these neurons have short neurites along each side of the foramen (Bader, 2007).
The close intermingling of axon endings of gustatory receptor neurons and arborizations of hugin neurons in the SOG suggested that hugin neurons could act as gustatory interneurons. One of the questions raised by the earlier study was to which class of hugin neurons these arborizations belonged. The current analysis suggests that all hugin neurons may have taste inputs; however, neurons that project to the protocerebrum are the only ones showing arborizations in the lateral part of the SOG, whereas other classes of neurons have distinct but overlapping neurites in the medial part of the SOG. Because the SOG lies in close proximity with the antennal lobes, the morphological relationship between the protocerebral hugin neurons and the antennal lobes, the first relay center for olfactory signaling, was investigated. It was first asked whether the arborizations of the protocerebral neurons overlapped with the antennal lobe. Protocerebrum-specific hugin clones in nc82 neuropile background staining indicated that the arborizations lie just at the border of the antennal lobe but do not intermingle with it. This is supported by clones in the adult, where the antennal lobes are significantly larger relative to the SOG. Next, the neurites to the larval protocerebum were analyzed with respect to the mushroom body calyx, a secondary olfactory relay center. Consistent with earlier results, the hugin neurites lie dorsal to the mushroom body calyx. Thus, at the morphological level, no overlap of hugin neurons with the central olfactory pathway is seen. However, insofar as hugin encodes a secreted peptide, an influence on the olfactory system cannot be excluded (Bader, 2007).
The arborizations of the protocerebral hugin neurons lie in a region lateral to the foramen that border the SOG. Other classes of hugin neurons do not show such arborization, but they all show neurites into a region directly juxtaposed to the foramen and the SOG. The architecture of the hugin neurons within this region indicates that the neurites lie in close proximity to each other. The ventral nerve cord neurons, the ring gland neurons, and the pharyngeal neurons all have neurites that extend just lateral to the foramen. For the ventral cord neuron, there is also a small arborization at the bottom end of the foramen, i.e., at the border to the SOG. For the pharyngeal neuron, two additional spiked neurites can be seen extending dorsally and ventrally in a similar region. Thus, in addition to having specific targets outside the SOG, the different hugin neurons have overlapping neurites near the SOG. These observations suggest that the region bordering the lateral foramen and the SOG might have a special role in mediating hugin neuronal function (Bader, 2007).
Out of several tested GAL4-drivers, two caused a marked reduction in the number of eclosed adults. These lines expressed GAL4 either under the ubiquitous tubulin or under a neuroblast-specific promoter. All the flies that had experienced ectopic hugin expression during development, were slightly smaller in size than the controls, otherwise they looked normal. In order to determine the lethal phase, eggs were collected, the number of hatchings was counted, and the development of the larvae was followed until pupariation. No significant differences in the hatching frequencies were noticed between any of the experimental and control crosses. Thus, the embryogenesis seems to proceed normally in the presence of ectopic hugin (Meng, 2002).
During larval development, the highest lethality was observed in larvae with the genotype UAS-hugin 8;tubP-GAL4, which carry two UAS-hugin insertions. Only 5% of the larvae survived until pupariation. The most prominent lethal phase, where 44% of all the larvae died, was around the second larval molt. Quite a few variations were observed between individuals in the precise time of death during the process. Earliest death was observed before the onset of ecdysis, when only duplicated mouth hooks and anterior spiracles were visible. The most advanced larvae had developed two complete cephalopharyngeal skeletons and almost completed ecdysis before dying, partly surrounded by the old cuticle (Meng, 2002).
In addition to the larvae, which simply arrested development, many exhibited defects in morphology and molting behaviour. Two major phenomena were observed: (1) larvae that had shed the old cuticle (partly or completely), but that were still attached to the old cephalopharyngeal skeleton were observed. This phenotype appears to be identical to the buttoned-up phenotype, that could induce it either by deletion of the ETH gene, or by premature injection of Drm-ETH-1. Normally, wild-type larvae always start the ecdysis process by shedding the cephalopharyngeal skeleton. (2) The larvae often developed brown spots on the new cuticle in a regular pattern late during the second instar. The heavily pigmented ones appeared unable to break the old second instar cuticle, although the cuticle with attached spiracles detached from the pigmented third instar cuticle. Instead, the larvae became trapped within a bag of old cuticle, in which they remained alive for some time. Some of these trapped larvae still had not developed a complete new set of the cephalopharyngeal skeleton. This phenomenon constitutes a novel phenotype. Of the larvae that survived through ecdysis, the majority (34% of all hatched larvae) died early during third instar. Taken together, these data suggest that ectopic hugin expression results in induction of premature ecdysis behaviour, which causes the death of the larva (Meng, 2002).
This suggests that at least one peptide encoded by the hugin gene is able to interact with the neuropeptide signalling pathway involved in the ecdysis process. Ecdysteroids are required for the initiation of the events leading to ecdysis, while the ecdysis behaviour itself is regulated by the neuropeptides. In Drosophila, double mouth hooks on larval corpses are considered to be the hallmark of failed ecdysis. Among the described mutants having the double mouthpart phenotype, many have defects in genes involved in ecdysone synthesis. Failed ecdysis is also caused by mutations in genes encoding neuropeptide-processing enzymes. ETH mutants exhibited an abnormal ecdysis behaviour, which often resulted in larvae that only partially managed to escape through an opening in the old cuticle, and which failed to detach their mouth hooks. The same phenomenon was seen in larvae with ectopic hugin expression (Meng, 2002).
Premature induction of ecdysis behaviour was induced by injection of Drm-ETH-1 and results in failed ecdysis, where the animals become trapped in the old cuticle. Hence, the absence as well as the presence of ETH at inappropriate time causes death through premature induction of the ecdysis behaviour. Ectopic hugin could likewise interfere with the ecdysis process, either through induction or inhibition of the ecdysis-signaling cascade. Indeed, the hugγ peptide has primary sequence resemblance to Drm-ETH-1 and could possibly be responsible for premature induction of ecdysis behaviour leading to the death of the larva. It has been experimentally shown that in addition to inducing factors, also inhibiting factors present in the suboesophageal ganglion play an important role during the ecdysis process, although such an inhibiting factor still remains to be identified. Either of the peptides encoded by hugin could be such a factor. However, further analyses are required to discriminate between the functions and the individual peptides in vivo (Meng, 2002).
A substantial proportion of the larvae died as young third instar larvae. This could be explained with reference to defects that arise during larval development due to prematurely induced but still successful ecdysis, the consequences of which are not fatal until after the molt. Another possibility is that a badly timed myostimulatory effect during normal ecdysis causes problems, which later kill the larva. Abnormal ecdysis can bring along several problems, for example in feeding and respiration, which could be the ultimate cause of death. Death could also be the consequence of cuticular defects. Observations of necrotic patches in the larval cuticula support this option. Less severely affected animals were able to complete ecdysis, but nevertheless died, maybe because the new cuticle did not sustain life. Previously, cuticular defects have been suggested to be the cause of death at the double mouth hook stage in larvae with ectopic FTZ-F1 expression and in larvae mutant for the sas cell surface receptor. A more direct link between cuticular defects and failed ecdysis has been demonstrated in an experiment where a chitin-synthesis inhibitor was fed to the larvae. Finally, it seems that hugin overexpression does not simply operate through the ecdysis control pathway. Eventually, hugin lack-of-function mutants will need to be created and analysed in order to establish the roles of the gene (Meng, 2002).
Reference names in red indicate recommended papers.
Search PubMed for articles about Drosophila Hugin
Austin, C., Lo, G., Nandha, K. A., Meleagros, L. and Bloom, S. R. (1995) Cloning and characterization of the cDNA encoding the human neuromedin U (NmU) precursor: NmU expression in the human gastrointestinal tract. J Mol Endocrinol 14: 157-169. Medline abstract: 7619205
Bader, R., et al. (2007). Genetic dissection of neural circuit anatomy underlying feeding behavior in Drosophila: distinct classes of hugin-expressing neurons. J. Comp. Neurol. 502(5):848-56. Medline abstract: 17436293
Gendre, N., et al. (2004). Integration of complex larval chemosensory organs into the adult nervous system of Drosophila. Development 131: 83-92. Medline abstract: 14645122
Melcher, C. and Pankratz. M. J. (2005). Candidate gustatory interneurons modulating feeding behavior in the Drosophila brain. PLoS Biol. 3(9):e305. Medline abstract: 16122349
Melcher, C., Bader, R., Walther, S., Simakov, O. and Pankratz, M. J. (2006). Neuromedin U and its putative Drosophila homolog hugin. PLoS Biol. 4(3):e68. Medline abstract: 16524341
Melcher, C., Bader, R. and Pankratz, M. J. (2007). Amino acids, taste circuits, and feeding behavior in Drosophila: towards understanding the psychology of feeding in flies and man. J. Endocrinol. 192(3): 467-72. Medline abstract: 17332516
Meng, X., et al. (2002). The Drosophila hugin gene codes for myostimulatory and ecdysis-modifying neuropeptides. Mech. Dev. 117(1-2): 5-13. Medline abstract: 12204246
Park, Y., Kim, Y. J. and Adams, M. E. (2002). Identification of G protein-coupled receptors for Drosophila PRXamide peptides, CCAP, corazonin, and AKH supports a theory of ligand-receptor coevolution. Proc. Natl. Acad. Sci. 99(17): 11423-8. Medline abstract: 12177421
Predel, R., et al. (1999). Differential distribution of pyrokinin-isoforms in cerebral and abdominal neurohemal organs of the American cockroach. Insect Biochem. Mol. Biol. 29: 139-144. Medline abstract: 10196736
Rosenkilde, C., et al. (2003). Molecular cloning, functional expression, and gene silencing of two Drosophila receptors for the Drosophila neuropeptide pyrokinin-2. BBRC 309: 485-494. Medline abstract: 12951076
Wang, Z., Singhvi, A., Kong, P. and Scott, K. (2004). Taste representations in the Drosophila brain. Cell 117: 981-991. Medline abstract: 15210117
date revised: 15 June 2007
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