Widespread employment of conserved C. elegans homeobox genes in neuronal identity specification.

Homeobox genes are prominent regulators of neuronal identity, but the extent to which their function has been probed in animal nervous systems remains limited. In the nematode Caenorhabditis elegans, each individual neuron class is defined by the expression of unique combinations of homeobox genes, prompting the question of whether each neuron class indeed requires a homeobox gene for its proper identity specification. We present here progress in addressing this question by extending previous mutant analysis of homeobox gene family members and describing multiple examples of homeobox gene function in different parts of the C.

The enteric nervous system of the pharynx is specified by the Sine oculis-like homeobox gene .

Overarching themes in the terminal differentiation of the enteric nervous system, an autonomously acting unit of animal nervous systems, have so far eluded discovery. We describe here the overall regulatory logic of enteric nervous system differentiation of the nematode that resides within the foregut (pharynx) of the worm. A homolog of the Sine oculis homeobox gene, , is expressed in all 14 classes of interconnected pharyngeal neurons from their birth throughout their life time, but in no other neuron type of the entire animal.

PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysms in humans.

Intracranial aneurysm (IA) rupture leads to subarachnoid hemorrhage, a sudden-onset disease that often causes death or severe disability. Although genome-wide association studies have identified common genetic variants that increase IA risk moderately, the contribution of variants with large effect remains poorly defined. Using whole-exome sequencing, we identified significant enrichment of rare, deleterious mutations in PPIL4, encoding peptidyl-prolyl cis-trans isomerase-like 4, in both familial and index IA cases.

Modular Organization of -regulatory Control Information of Neurotransmitter Pathway Genes in .

We explore here the -regulatory logic that dictates gene expression in specific cell types in the nervous system. We focus on a set of eight genes involved in the synthesis, transport, and breakdown of three neurotransmitter systems: acetylcholine (, , , and ), glutamate (), and γ-aminobutyric acid (, , and ). These genes are specifically expressed in defined subsets of cells in the nervous system.

Renal involvement in patients with mucolipidosis IIIalpha/beta: Causal relation or co-occurrence?

Mucolipidosis IIIalpha/beta (MLIIIalpha/beta) is a rare lysosomal storage disorder characterized by childhood onset of flexion contractures of fingers, joint stiffness in the shoulders, hips, and knees, and mild short stature. Recessive mutations in the GNPTAB gene have been associated with MLIIIalpha/beta. We present five children aged 9-16 years from a large kindred family whose serum activities of several lysosomal enzymes were significantly elevated.

Integrated genomic characterization of IDH1-mutant glioma malignant progression.

Gliomas represent approximately 30% of all central nervous system tumors and 80% of malignant brain tumors. To understand the molecular mechanisms underlying the malignant progression of low-grade gliomas with mutations in IDH1 (encoding isocitrate dehydrogenase 1), we studied paired tumor samples from 41 patients, comparing higher-grade, progressed samples to their lower-grade counterparts. Integrated genomic analyses, including whole-exome sequencing and copy number, gene expression and DNA methylation profiling, demonstrated nonlinear clonal expansion of the original tumors and identified oncogenic pathways driving progression.