Neural Circuit Mechanisms Underlying Behavioral Evolution in Drosophila

Courtship rituals serve to reinforce reproductive barriers between closely related species. Several species in the Drosophila melanogaster subgroup exhibit pre-mating isolation due, in part, to the fact that D. melanogaster females produce 7,11-heptacosadiene (7,11-HD), a pheromone that promotes courtship in D. melanogaster males but suppresses it in D. simulans, D. yakuba, and D. erecta males. Here we compare pheromone-processing pathways across species to define how males endow 7,11-HD with the opposite behavioral valence to underlie species discrimination. We first show that D. melanogaster and D. simulans males detect 7,11-HD using the homologous peripheral sensory neurons, but this signal is differentially propagated to the P1 neurons that control courtship behavior. A change in the balance of excitation and inhibition onto courtship-promoting neurons transforms an excitatory pheromonal cue in D. melanogaster into an inhibitory one in D. simulans. Our results reveal how species-specific pheromone responses can emerge from conservation of peripheral detection mechanisms and diversification of central circuitry and suggest how evolution can exploit flexible circuit nodes to generate behavioral variation. To investigate if changes in the balance of excitation and inhibition at this node evolved repeatedly, we began characterizing the pheromone processing pathways in D. yakuba and D. erecta, two species we believe derived their aversion to 7,11-HD independently from D. simulans. This comparison provides a rare opportunity to explore the neural basis for parallel behavioral evolution. Finally, we observed differences in the olfactory and gustatory pathways D. melanogaster and D. simulans males use for sex discrimination. In males of both species, the male-specific volatile pheromone, cVA, activates a conserved sensory pathways and suppresses male courtship. However, 7-T, the major cuticular pheromone produced by all males in the D. melanogaster subgroup and by D. simulans females, plays a differential role in regulating male courtship across species – 7-T suppresses courtship in D. melanogaster males, but neither promotes nor inhibits courtship in D. simulans males. A difference in either detection of 7-T by peripheral sensory neurons or propagation of this signal to higher brain regions results in this pheromone activating courtship-suppressing mAL neurons in D. melanogaster males, but not D. simulans males. Together, these studies represent the first systematic comparison of neural circuits across Drosophila species and mark a new advance in the study of behavioral evolution by revealing how changes in central circuitry can alter discrete behaviors

Patterns of Diversification in a Neotropical Radiation of Birds (Aves: Furnariidae)

Ecology and the role of natural selection in lineage diversification has been a central topic in evolutionary biology since Darwin. At the macroevolutionary scale, this idea is embodied in the ecological theory of adaptive radiation, which posits that rapid diversification is driven by ecological adaptive radiation in which speciation is coupled with niche divergence. Within species, the theory of ecological speciation proposes that local adaptation drives speciation by reducing gene flow among populations occupying different environments either by directly reducing migration or by reducing the fitness of migrants. Much progress has been made testing these predictions in a multitude of organisms, but there remains a lack of studies addressing the role of ecology in diversification at multiple evolutionary scales within the same lineage. Herein, I use the Neotropical bird radiation of ovenbirds (Passeriformes: Furnariidae) as a model system to examine the role of ecology in speciation and lineage diversification. I show that, across furnariid subclades, rates of lineage diversification are best predicted by the rate of climatic-niche evolution rather than ecomorphological evolution, although both are clearly important. This result is consistent with a role for environmental gradients in driving speciation through the process of isolation-by-adaptation (IBA). I then compared the relative support for IBA against the null model of isolation-by-distance (IBD) in a species of furnariid, Cranioleuca antisiensis, that shows signs of incipient speciation and is distributed across a broad environmental gradient. Using genetic, phenotypic, and environmental data from across its distribution, I found evidence of local adaptation in body size. However, I found that IBD was the best explanation for genetic differentiation along the cline, suggesting a limited role for the environmental gradient in reducing gene flow among populations of C. antisiensis. Finally, I explore the properties of the speciation mechanism ‘speciation-by-extinction’. Speciation-by-extinction (SBE) is an alternative to the standard model of allopatric speciation where speciation results from divergence accrued following the isolation of two undifferentiated populations. SBE, in contrast, proposes that speciation can result from the partitioning of standing phenotypic or genetic variation through the local extinction of intermediate populations

Alternative splicing of MALT1 controls signalling and activation of CD4+ T cells

MALT1 channels proximal T-cell receptor (TCR) signalling to downstream signalling pathways. With MALT1A and MALT1B two conserved splice variants exist and we demonstrate here that MALT1 alternative splicing supports optimal T-cell activation. Inclusion of exon7 in MALT1A facilitates the recruitment of TRAF6, which augments MALT1 scaffolding function, but not protease activity. Naive CD4+ T cells express almost exclusively MALT1B and MALT1A expression is induced by TCR stimulation. We identify hnRNP U as a suppressor of exon7 inclusion. Whereas selective depletion of MALT1A impairs T-cell signalling and activation, downregulation of hnRNP U enhances MALT1A expression and T-cell activation. Thus, TCR-induced alternative splicing augments MALT1 scaffolding to enhance downstream signalling and to promote optimal T-cell activation

Neuroendocrine cells initiate protective upper airway reflexes

Airway neuroendocrine (NE) cells have been proposed to serve as specialized sensory epithelial cells that modulate respiratory behavior by communicating with nearby nerve endings. However, their functional properties and physiological roles in the healthy lung, trachea, and larynx remain largely unknown. In this work, we show that murine NE cells in these compartments have distinct biophysical properties but share sensitivity to two commonly aspirated noxious stimuli, water and acid. Moreover, we found that tracheal and laryngeal NE cells protect the airways by releasing adenosine 5'-triphosphate (ATP) to activate purinoreceptive sensory neurons that initiate swallowing and expiratory reflexes. Our work uncovers the broad molecular and biophysical diversity of NE cells across the airways and reveals mechanisms by which these specialized excitable cells serve as sentinels for activating protective responses

SAP97 Binding Partner CRIPT Promotes Dendrite Growth <i>in Vitro</i> and <i>in Vivo</i>

The dendritic tree is a key determinant of neuronal information processing. In the motor system, the dendritic tree of spinal cord neurons undergoes dramatic remodeling in an activity-dependent manner during early postnatal life. This leads to the proper segmental spinal cord connectivity that subserves normal locomotor behavior. One molecular system driving the establishment of dendrite architecture of mammalian motor neurons relies on AMPA receptors assembled with the GluA1 subunit and this occurs in an NMDA-R- independent manner. The dendrite growth promoting activity of GluA1-containing AMPA receptors depends on its intracellular binding partner, SAP97, and SAP97’s PDZ3 domain. We show here that CRIPT is a bona fide SAP97 PDZ3-domain binding partner, localizes to synapses with GluA1 and SAP97 along the dendritic tree and is a determinant of the dendritic growth of mammalian spinal cord neurons. We further show that CRIPT has a well-conserved ortholog in the nematode, Caenorhabditis elegans, and animals lacking CRIPT display decreased dendrite branching of the well-studied PVD neuron in vivo. The lack of CRIPT leads to a selective defect in touch perception and this is rescued by expression of wild type human CRIPT in the nervous system. This work brings new light into the molecular machinery that drives dendritic growth during development and may prove relevant to the promotion of nervous system plasticity following insult.Significance Statement Proper dendritic growth is a critical step in the development of neuronal connectivity that underlies proper neuronal communication. Much is known about how NMDA receptors drive neuronal development and plasticity, but less is known about how AMPA receptors contribute in an independent manner. While SAP97 plays a critical role in this process, the molecular mechanisms and binding partners that subserve these effects are under active exploration. Here we show that the cysteine-rich interactor of PDZ3 (CRIPT) is a bona fide binding partner of SAP97 in biochemical assays and resides in dendrites in the vicinity of putative AMPAergic synapses. In knockdown experiments, we find that CRIPT is essential for SAP97-dependent dendrite growth in vitro. We extend these studies to an in vivo model and show that CRIPT is also essential for dendrite growth and mechanosensory function in C.elegans. This work links AMPA receptors, MAGUKs and CRIPT to essential neuronal cell biology and C.elegans behavior

Periodic vs. intermittent adaptive cycles in quasispecies co-evolution

We study an abstract model for the co-evolution between mutating viruses and the adaptive immune system. In sequence space, these two populations are localized around transiently dominant strains. Delocalization or error thresholds exhibit a novel interdependence because immune response is conditional on the viral attack. An evolutionary chase is induced by stochastic fluctuations and can occur via periodic or intermittent cycles. Using simulations and stochastic analysis, we show how the transition between these two dynamic regimes depends on mutation rate, immune response, and population size.Comment: 5 pages, 3 figures, 11 pages supplementary material; updated formatting; accepted at Phys. Rev. Let