Yki/YAP, Sd/TEAD and Hth/MEIS Control Tissue Specification in the Drosophila Eye Disc Epithelium

During animal development, accurate control of tissue specification and growth are critical to generate organisms of reproducible shape and size. The eye-antennal disc epithelium of Drosophila is a powerful model system to identify the signaling pathway and transcription factors that mediate and coordinate these processes. We show here that the Yorkie (Yki) pathway plays a major role in tissue specification within the developing fly eye disc epithelium at a time when organ primordia and regional identity domains are specified. RNAi-mediated inactivation of Yki, or its partner Scalloped (Sd), or increased activity of the upstream negative regulators of Yki cause a dramatic reorganization of the eye disc fate map leading to specification of the entire disc epithelium into retina. On the contrary, constitutive expression of Yki suppresses eye formation in a Sd-dependent fashion. We also show that knockdown of the transcription factor Homothorax (Hth), known to partner Yki in some developmental contexts, also induces an ectopic retina domain, that Yki and Scalloped regulate Hth expression, and that the gain-of-function activity of Yki is partially dependent on Hth. Our results support a critical role for Yki- and its partners Sd and Hth - in shaping the fate map of the eye epithelium independently of its universal role as a regulator of proliferation and survival

Yki/YAP, Sd/TEAD and Hth/MEIS Control Tissue Specification in the Drosophila Eye Disc Epithelium

During animal development, accurate control of tissue specification and growth are critical to generate organisms of reproducible shape and size. The eye-antennal disc epithelium of Drosophila is a powerful model system to identify the signaling pathway and transcription factors that mediate and coordinate these processes. We show here that the Yorkie (Yki) pathway plays a major role in tissue specification within the developing fly eye disc epithelium at a time when organ primordia and regional identity domains are specified. RNAi-mediated inactivation of Yki, or its partner Scalloped (Sd), or increased activity of the upstream negative regulators of Yki cause a dramatic reorganization of the eye disc fate map leading to specification of the entire disc epithelium into retina. On the contrary, constitutive expression of Yki suppresses eye formation in a Sd-dependent fashion. We also show that knockdown of the transcription factor Homothorax (Hth), known to partner Yki in some developmental contexts, also induces an ectopic retina domain, that Yki and Scalloped regulate Hth expression, and that the gain-of-function activity of Yki is partially dependent on Hth. Our results support a critical role for Yki- and its partners Sd and Hth - in shaping the fate map of the eye epithelium independently of its universal role as a regulator of proliferation and survival

Percutaneous Intradiscal Aspiration of a Lumbar Vacuum Disc Herniation: A Case Report

We report a case of an 83-year-old gentleman presenting with acute low back pain and radicular left lower extremity pain after golfing. A magnetic resonance imaging (MRI) of the lumbar spine revealed a low-signal-density lesion compressing the L5 nerve. A computed tomography scan was then ordered, confirming an extra-foraminal disc protrusion at the L5–S1 level, containing a focus of gas that was compressing the left L5 nerve root and communicating with the vacuum disc at L5–S1. After a failed left L5 transforaminal epidural steroid injection, the patient was brought back for a percutaneous intradiscal aspiration of the vacuum disc gas. This resulted in immediate relief for the patient. A follow-up MRI performed 2 months after the procedure found an approximate 25% reduction in the size of the vacuum disc herniation. Six months after the procedure, the patient remains free of radicular pain. This case report suggests that a percutaneous aspiration of gas from a vacuum disc herniation may assist in the treatment of radicular pain

Common variant at 16p11.2 conferring risk of psychosis.

Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders)

Parthenogenesis in insects: the centriole renaissance

Building a new organism usually requires the contribution of two differently shaped haploid cells, the male and female gametes, each providing its genetic material to restore diploidy of the new born zygote. The successful execution of this process requires defined sequential steps that must be completed in space and time. Otherwise, development fails. Relevant among the earlier steps are pronuclear migration and formation of the first mitotic spindle that promote the mixing of parental chromosomes and the formation of the zygotic nucleus. A complex microtubule network ensures the proper execution of these processes. Instrumental to microtubule organization and bipolar spindle assembly is a distinct non-membranous organelle, the centrosome. Centrosome inheritance during fertilization is biparental, since both gametes provide essential components to build a functional centrosome. This model does not explain, however, centrosome formation during parthenogenetic development, a special mode of sexual reproduction in which the unfertilized egg develops without the contribution of the male gamete. Moreover, whereas fertilization is a relevant example in which the cells actively check the presence of only one centrosome, to avoid multipolar spindle formation, the development of parthenogenetic eggs is ensured, at least in insects, by the de novo assembly of multiple centrosomes. Here, we will focus our attention on the assembly of functional centrosomes following fertilization and during parthenogenetic development in insects. Parthenogenetic development in which unfertilized eggs are naturally depleted of centrosomes would provide a useful experimental system to investigate centriole assembly and duplication together with centrosome formation and maturation