The RNA-binding protein ELAV regulates Hox RNA processing, expression and function within the Drosophila nervous system

The regulated head-to-tail expression of Hox genes provides a coordinate system for the activation of specific programmes of cell differentiation according to axial level. Recent work indicates that Hox expression can be regulated via RNA processing but the underlying mechanisms and biological significance of this form of regulation remain poorly understood. Here we explore these issues within the developing Drosophila central nervous system (CNS). We show that the pan-neural RNA-binding protein (RBP) ELAV (Hu antigen) regulates the RNA processing patterns of the Hox gene Ultrabithorax (Ubx) within the embryonic CNS. Using a combination of biochemical, genetic and imaging approaches we demonstrate that ELAV binds to discrete elements within Ubx RNAs and that its genetic removal reduces Ubx protein expression in the CNS leading to the respecification of cellular subroutines under Ubx control, thus defining for the first time a specific cellular role of ELAV within the developing CNS. Artificial provision of ELAV in glial cells (a cell type that lacks ELAV) promotes Ubx expression, suggesting that ELAVdependent regulation might contribute to cell type-specific Hox expression patterns within the CNS. Finally, we note that expression of abdominal A and Abdominal B is reduced in elav mutant embryos, whereas other Hox genes (Antennapedia) are not affected. Based on these results and the evolutionary conservation of ELAV and Hox genes we propose that the modulation of Hox RNA processing by ELAV serves to adapt the morphogenesis of the CNS to axial level by regulating Hox expression and consequently activating local programmes of neural differentiation

A common genetic target for environmental and heritable influences on aggressiveness in Drosophila

Environmental and genetic factors can modulate aggressiveness, but the biological mechanisms underlying their influence are largely unknown. Social experience with conspecifics suppresses aggressiveness in both vertebrate and invertebrate species, including Drosophila. We searched for genes whose expression levels correlate with the influence of social experience on aggressiveness in Drosophila by performing microarray analysis of head tissue from socially isolated (aggressive) vs. socially experienced (nonaggressive) male flies. Among {approx}200 differentially expressed genes, only one was also present in a gene set previously identified by profiling Drosophila strains subjected to genetic selection for differences in aggressiveness [Dierick HA, Greenspan RJ (2006) Nat Genet 38:1023–1031]. This gene, Cyp6a20, encodes a cytochrome P450. Social experience increased Cyp6a20 expression and decreased aggressiveness in a reversible manner. In Cyp6a20 mutants, aggressiveness was increased in group-housed but not socially isolated flies. These data identify a common genetic target for environmental and heritable influences on aggressiveness. Cyp6a20 is expressed in a subset of nonneuronal support cells associated with pheromone-sensing olfactory sensilla, suggesting that social experience may influence aggressiveness by regulating pheromone sensitivity

The Potential of Global Payment: Insights From the Field

Offers experts' views on the advantages and limitations of improved models of capitation in addressing healthcare costs and quality. Recommends phased and tailored implementation, adoption by Medicare, and considerations for forms and amounts of payment

Empathising and systemising in adolescents with gender dysphoria

Background: Recent studies have highlighted the co-occurrence of gender dysphoria (GD) in adolescence and Autistic Spectrum Conditions (ASC). Systemising and empathising are two psychological dimensions linked to ASC. People with ASC score below average on the Empathy Quotient (EQ) and average or above average on the Systemising Quotient (SQ). Based on the results of previous studies we predicted that if the young people with GD shared aspects of the ‘broader autism phenotype’, their EQ would be lower, and their SQ would be the same or higher, compared to controls of their natal gender. Methods: This preliminary study examined systemising and empathising in adolescents with GD using parent report questionnaires. 35 parents of adolescents with GD aged 12-18 attending the Gender Identity Development Service (London) took part. Parents of 156 typically developing adolescents aged 12-18 were used as a control group. The parents were asked to complete the Adolescent EQ and SQ. Results: The mean EQ score of both the female-to-male, and male-to-female GD group was found to be significantly lower than typically developing females, but similar to that of control males. There was no significant difference on the SQ between the gender dysphoric groups and either female or male controls. Conclusion: This study shows that on average adolescents with GD, specifically those who are female-to-male, have lower empathy than controls. For this group of adolescents it may be helpful to offer psychological interventions that improve their communication skills and their ability to take on board other people’s views, to support their development. This may enable them to make better informed decisions regarding treatment and physical intervention options during adolescence and beyond

The unfulfilled gene is required for the development of mushroom body neuropil in Drosophila

<p>Abstract</p> <p>Background</p> <p>The mushroom bodies (MBs) of <it>Drosophila </it>are required for complex behaviors and consist of three types of neurons, γ, α'/β' and α/β. Previously, roles for transcription factors in MB neuronal differentiation have only been described for a subset of MB neurons. We are investigating the roles of <it>unfulfilled </it>(<it>unf</it>; <it>HR51</it>, CG16801) in MB development. <it>unf </it>encodes a nuclear receptor that is orthologous to the nuclear receptors fasciculation of axons defective 1 (FAX-1) of the nematode and photoreceptor specific nuclear receptor (PNR) of mammals. Based on our previous observations that <it>unf </it>transcripts accumulate in MB neurons at all developmental stages and the presence of axon pathfinding defects in <it>fax-1 </it>mutants, we hypothesized that <it>unf </it>regulates MB axon growth and pathfinding.</p> <p>Results</p> <p>We show that <it>unf </it>mutants exhibit a range of highly penetrant axon stalling phenotypes affecting all neurons of the larval and adult MBs. Phenotypic analysis of <it>unf</it>^{<it>X1 </it>}mutants revealed that α'/β' and α/β neurons initially project axons but stall prior to the formation of medial or dorsal MB lobes. <it>unf</it>^{<it>Z0001 </it>}mutants form medial lobes, although these axons fail to branch, which results in a failure to form the α or α' dorsal lobes. In either mutant background, γ neurons fail to develop larval-specific dorsal projections. These mutant γ neurons undergo normal pruning, but fail to re-extend axons medially during pupal development. <it>unf</it>^{<it>RNAi </it>}animals displayed phenotypes similar to those seen in <it>unf</it>^{<it>Z0001 </it>}mutants. Unique asymmetrical phenotypes were observed in <it>unf</it>^<it>X1</it>/<it>unf</it>^{<it>Z0001 </it>}compound heterozygotes. Expression of <it>UAS-unf </it>transgenes in MB neurons rescues the larval and adult <it>unf </it>mutant phenotypes.</p> <p>Conclusions</p> <p>These data support the hypothesis that <it>unf </it>plays a common role in the development of all types of MB neurons. Our data indicate that <it>unf </it>is necessary for MB axon extension and branching and that the formation of dorsal collaterals is more sensitive to the loss of <it>unf </it>function than medial projections. The asymmetrical phenotypes observed in compound heterozygotes support the hypothesis that the earliest MB axons may serve as pioneers for the later-born MB neurons, providing evidence for pioneer MB axon guidance in post-embryonic development.</p

Meinhard Robinow: An appreciation

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38264/1/1320590103_ftp.pd

Metacarpophalangeal pattern profile analysis in Robinow syndrome

We analyzed the metacarpophalangeal pattern profile (MCPP) on 15 individuals with Robinow syndrome and calculated a mean Robinow syndrome profile. Correlation studies confirm clinical homogeneity of the hand profile in the Robinow syndrome. Discriminant analysis of individuals with Robinow syndrome compared with a sample of normal individuals produces a function of 6 MCPP variable that may provide a useful tool for diagnosis