An extracellular adhesion molecule complex patterns dendritic branching and morphogenesis.

Robust dendrite morphogenesis is a critical step in the development of reproducible neural circuits. However, little is known about the extracellular cues that pattern complex dendrite morphologies. In the model nematode Caenorhabditis elegans, the sensory neuron PVD establishes stereotypical, highly branched dendrite morphology.

The transmembrane LRR protein DMA-1 promotes dendrite branching and growth in C. elegans.

Dendrites often adopt complex branched structures. The development and organization of these arbors fundamentally determine the potential input and connectivity of a given neuron. The cell-surface receptors that control dendritic branching remain poorly understood.

Systematic genetic analysis of virulence in the human fungal pathogen Cryptococcus neoformans.

The fungus Cryptococcus neoformans is a leading cause of mortality and morbidity among HIV-infected individuals. We utilized the completed genome sequence and optimized methods for homologous DNA replacement using high-velocity particle bombardment to engineer 1201 gene knockout mutants. We screened this resource in vivo for proliferation in murine lung tissue and in vitro for three well-recognized virulence attributes-polysaccharide capsule formation, melanization, and growth at body temperature.

Exploration of whole-genome responses of the human AIDS-associated yeast pathogen Cryptococcus neoformans var grubii: nitric oxide stress and body temperature.

Cryptococcus neoformans var grubii is an opportunistic basidiomycete yeast pathogen that is a significant cause of HIV/AIDS-related deaths worldwide. We describe a whole-genome oligonucleotide microarray for this pathogen. These arrays have been used to elucidate the transcriptional responses of the genome to heat shock as well as to two conditions relevant to human infections: body temperature and nitric oxide (NO) stress produced by the NO donor DPTA-NONOate.

Parallel beta-helix proteins required for accurate capsule polysaccharide synthesis and virulence in the yeast Cryptococcus neoformans.

The principal capsular polysaccharide of the opportunistic fungal pathogen Cryptococcus neoformans consists of an alpha-1,3-linked mannose backbone decorated with a repeating pattern of glucuronyl and xylosyl side groups. This structure is critical for virulence, yet little is known about how the polymer, called glucuronoxylomannan (GXM), is faithfully synthesized and assembled. We have generated deletions in two genes encoding predicted parallel beta-helix repeat proteins, which we have designated PBX1 and PBX2.

A link between virulence and homeostatic responses to hypoxia during infection by the human fungal pathogen Cryptococcus neoformans.

Fungal pathogens of humans require molecular oxygen for several essential biochemical reactions, yet virtually nothing is known about how they adapt to the relatively hypoxic environment of infected tissues. We isolated mutants defective in growth under hypoxic conditions, but normal for growth in normoxic conditions, in Cryptococcus neoformans, the most common cause of fungal meningitis. Two regulatory pathways were identified: one homologous to the mammalian sterol-response element binding protein (SREBP) cholesterol biosynthesis regulatory pathway, and the other a two-component-like pathway involving a fungal-specific hybrid histidine kinase family member, Tco1.