Vitiligo repigmentation is a complex process in which the melanocyte-depleted interfollicular epidermis is repopulated by melanocyte precursors from hair follicle bulge that proliferate, migrate, and differentiate into mature melanocytes on their way to the epidermis. The strongest stimulus for vitiligo repigmentation is narrow-band UVB (NBUVB), but how the hair follicle melanocyte precursors are activated by UV light has not been extensively studied. To better understand this process, we developed an application that combined laser capture microdissection and subsequent whole transcriptome RNA sequencing of hair follicle bulge melanocyte precursors and compared their gene signatures to that of regenerated mature epidermal melanocytes from NBUVB-treated vitiligo skin. Using this strategy, we found up-regulation of TNC, GJB6, and THBS1 in the hair follicle bulge melanocytes and of TYR in the epidermal melanocytes of the NBUVB-treated vitiligo skin. We validated these results by quantitative real-time-PCR using NBUVB-treated vitiligo skin and untreated normal skin. We also identified that GLI1, a candidate stem cell-associated gene, is significantly up-regulated in the melanocytes captured from NBUVB-treated vitiligo bulge compared with untreated vitiligo bulge. These signals are potential key players in the activation of bulge melanocyte precursors during vitiligo repigmentation.

27Despite the conserved function of aggression across taxa in obtaining critical 28 resources such as food and mates, serotonin's (5-HT) modulatory role on29 aggressive behavior appears to be largely inhibitory for vertebrates but stimulatory 30 for invertebrates. However, critical gaps exist in our knowledge of invertebrates that 31 need to be addressed before definitively stating opposing roles for 5-HT and 32 aggression. Specifically, the role of 5-HT receptor subtypes are largely unknown, as 33 is the potential interactive role of 5-HT with other neurochemical systems known to 34 play a critical role in aggression. Similarly, the influence of these systems in driving 35 sex differences in aggressive behavior of invertebrates is not well understood. Here, 36 we investigated these questions by employing complementary approaches in a 37 novel invertebrate model of aggression, the stalk-eyed fly. A combination of altered 38 social conditions, pharmacological manipulation and 5-HT 2 receptor knockdown by 39 siRNA revealed an inhibitory role of this receptor subtype on aggression.40 Additionally, we provide evidence for 5-HT 2 's involvement in regulating neuropeptide 41 F activity, a suspected inhibitor of aggression. However, this function appears to be 42 stage-specific, altering only the initiation stage of aggressive conflicts. Alternatively, 43 pharmacologically increasing systemic concentrations of 5-HT significantly elevated 44 the expression of the neuropeptide tachykinin, which did not affect contest initiation 45 but instead promoted escalation via production of high intensity aggressive 46 behaviors. Notably, these effects were limited solely to males, with female 47 aggression and neuropeptide expression remaining unaltered by any manipulation 3 48 that affected 5-HT. Together, these results demonstrate a more nuanced role for 5-49 HT in modulating aggression in invertebrates, revealing an important interactive role 50 with neuropeptides that is more reminiscent of vertebrates. The sex-differences 51 described here also provide valuable insight into the evolutionary contexts of this 52 complex behavior. 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 4 71 1. Introduction 72 73Serotonin (5-HT) appears to promote aggression in invertebrates (1,2), in 74 contrast to the largely inhibitory effect seen in vertebrates (3, but see 4). Much of 75 the empirical support for this dichotomy comes from studies using arthropod 76 invertebrates, with increased expression of overt aggressive behavior and greater 77 willingness to engage in conflict seen in decapod crustaceans (5-8), crickets (9), 78 ants (10,11), and dipteran flies (12-15) following pharmacological or genetic 79 elevations of 5-HT at the systemic level. While these findings support the 80 presumption that 5-HT has opposing effects on invertebrate aggression from 81 vertebrates, there are critical gaps in knowledge that need to be considered before 82 accurately stating that 5-HT exclusively modulates invertebrate aggression in a 83 positive mann...

No abstract

Despite the conserved function of aggression across taxa in obtaining critical resources such as food and mates, serotonin’s (5-HT) modulatory role on aggressive behavior appears to be largely inhibitory for vertebrates but stimulatory for invertebrates. However, critical gaps exist in our knowledge of invertebrates that need to be addressed before definitively stating opposing roles for 5-HT and aggression. Specifically, the role of 5-HT receptor subtypes are largely unknown, as is the potential interactive role of 5-HT with other neurochemical systems known to play a critical role in aggression. Similarly, the influence of these systems in driving sex differences in aggressive behavior of invertebrates is not well understood. Here, we investigated these questions by employing complementary approaches in a novel invertebrate model of aggression, the stalk-eyed fly. A combination of altered social conditions, pharmacological manipulation and 5-HT2 receptor knockdown by siRNA revealed an inhibitory role of this receptor subtype on aggression. Additionally, we provide evidence for 5-HT2’s involvement in regulating neuropeptide F activity, a suspected inhibitor of aggression. However, this function appears to be stage-specific, altering only the initiation stage of aggressive conflicts. Alternatively, pharmacologically increasing systemic concentrations of 5-HT significantly elevated the expression of the neuropeptide tachykinin, which did not affect contest initiation but instead promoted escalation via production of high intensity aggressive behaviors. Notably, these effects were limited solely to males, with female aggression and neuropeptide expression remaining unaltered by any manipulation that affected 5-HT. Together, these results demonstrate a more nuanced role for 5-HT in modulating aggression in invertebrates, revealing an important interactive role with neuropeptides that is more reminiscent of vertebrates. The sex-differences described here also provide valuable insight into the evolutionary contexts of this complex behavior.

No abstract