Ablation of various regions within the avian vagal neural crest has differential effects on ganglion formation in the fore‐, mid‐ and hindgut

The vagal neural crest adjacent to the first seven somites gives rise to both ganglionic and ectomesenchymal derivatives. Ganglionic derivatives are the neurons and supportive cells of the enteric nervous system (ENS), cardiac, and dorsal root ganglia. Ectomesenchymal derivatives are cells in the cardiac outflow tract and the mesenchymal components of thymus and parathyroids. Ectomesenchymal derivatives are formed by a segment of the vagal neural crest, from the level of the otic vesicle down to the caudal boundary of the third somite, called the cardiac neural crest. We performed neural crest ablations to study regional differences within the avian vagal neural crest with regard to the formation of the ENS. Ablation of the entire vagal neural crest from the mid‐otic vesicle down to the seventh somite plus the nodose placode resulted in the absence of ganglia in the midgut (jejunum and ileum) and hindgut (colon). The foregut (esophagus, proventriculus, gizzard, and duodenum) was normally innervated. After ablation of the vagal neural crest adjacent to somites 3–5, ganglia were absent in the hindgut. Ablations of vagal neural crest not including this segment had no effect on the formation of the ENS. We surmise that the innervation of the hindgut in vivo depends specifically on the neural crest adjacent to somites 3–5, whereas innervation of the midgut can be accomplished by all segments within the vagal neural crest. The foregut can also be innervated by a source outside the vagal neural crest. To study intrinsic differences between various vagal neural crest segments regarding ENS formation, we performed chorioallantoic membrane cocultures of segments of quail vagal neural anlage and E4 chicken hindgut. We found that all vagal neural crest segments were able to give rise to enteric ganglia in the hindgut. When the neural crest of somites 6 and 7 was included in the segment, we also found melanocytes in the hindgut, suggesting that this segment is more related to trunk neural crest. Furthermore, we found that the vagal neural anlage from older embryos (>18 somites) showed an increased potential to form enteric ganglia. This suggests that vagal neural crest cells that have been in prolonged contact with the neural tube in vivo, because of either late emigration or delayed migration, have an increased probability to form enteric ganglia

Copy number variation in obsessive-compulsive disorder and tourette syndrome: A cross-disorder study

Objective Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. Method The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. Results Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p =.09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0 control deletions, p =.08 in the current study, p =.025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support for the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in individuals with autism or schizophrenia (2-4%). Conclusion Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes