Molecular topography of an entire nervous system.

We have produced gene expression profiles of all 302 neurons of the C. elegans nervous system that match the single-cell resolution of its anatomy and wiring diagram. Our results suggest that individual neuron classes can be solely identified by combinatorial expression of specific gene families.

In silico analysis of the transcriptional regulatory logic of neuronal identity specification throughout the nervous system.

The generation of the enormous diversity of neuronal cell types in a differentiating nervous system entails the activation of neuron type-specific gene batteries. To examine the regulatory logic that controls the expression of neuron type-specific gene batteries, we interrogate single cell expression profiles of all 118 neuron classes of the nervous system for the presence of DNA binding motifs of 136 neuronally expressed transcription factors. Using a phylogenetic footprinting pipeline, we identify regulatory motif enrichments among neuron class-specific gene batteries and we identify cognate transcription factors for 117 of the 118 neuron classes.

The stress-responsive gene GDPGP1/mcp-1 regulates neuronal glycogen metabolism and survival.

Maladaptive responses to stress might play a role in the sensitivity of neurons to stress. To identify novel cellular responses to stress, we performed transcriptional analysis in acutely stressed mouse neurons, followed by functional characterization in Caenorhabditis elegans. In both contexts, we found that the gene GDPGP1/mcp-1 is down-regulated by a variety of stresses.

Alzheimer's disease: presence and role of microRNAs.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for the most cases of dementia. AD affects more than 25 million people globally and is predicted to affect nearly one in 85 people worldwide by 2050. AD is characterized by the accumulation of dense plaques of β-amyloid peptide (Aβ) and neurofibrillary tangles of hyperphosphorylated tau that cause impairment in memory, cognition, and daily activities.