The C. elegans ALA neuron : its transcriptome and role in inducing sleep

A long-standing yet to be accomplished task in understanding behavior is to dissect the function of each gene involved in the development and function of a neuron. The C. elegans ALA neuron was chosen in this study for its known function in sleep, an ancient but less understood animal behavior. Single-cell transcriptome profiling identified 8,133 protein-coding genes in the ALA neuron, of which 57 are neuropeptide-coding genes. The most enriched genes are also neuropeptides. In combination with gain-of-function and loss-of-function assays, here I showed that the ALA-enriched FMRFamide neuropeptides, FLP-7, FLP-13, and FLP-24, are sufficient and necessary for inducing C. elegans sleep. These neuropeptides act as neuromodulators through GPCRs, NPR-7, and NPR-22. Further investigation in zebrafish indicates that FMRFamide neuropeptides are sleep-promoting molecules in animals. To correlate the behavioral outputs with genomic context, I constructed a gene regulatory network of the relevant genes controlling C. elegans sleep behavior through EGFR signaling in the ALA neuron. First, I identified an ALA cell-specific motif to conduct a genome-wide search for possible ALA-expressed genes. I then filtered out non ALA-expressed genes by comparing the motif-search genes with ALA transcriptomes from single-cell profiling. In corroborating with ChIP-seq data from modENCODE, I sorted out direct interaction of ALA-expressed transcription factors and differentiation genes in the EGFR sleep regulation pathway. This approach provides a network reference for the molecular regulation of C. elegans sleep behavior, and serves as an entry point for the understanding of functional genomics in animal behaviors.

Representing measures on the Royden boundary for solutions of Δu=Pu on a Riemannian manifold

Consider the Royden compactification R* of a Riemannian n-manifold R, Γ = R*\R its Royden boundary, Δ its harmonic boundary and the elliptic differential equation Δu = Pu, P ≥ 0 on R. A regular Borel measure m^P can be constructed on Γ with support equal to the closure of Δ^P = {q ϵ Δ : q has a neighborhood U in R* with _U^ʃ_ᴖR^{P ˂ ∞} }. Every enegy-finite solution to u (i.e. E(u) = D(u) + ^ʃ_Ru²P ˂ ∞, where D(u) is the Dirichlet integral of u) can be represented by u(z) = ^ʃ_Γu(q)K(z,q)dm^P(q) where K(z,q) is a continuous function on ^Rx Γ . A _P^~_E-function is a nonnegative solution which is the infimum of a downward directed family of energy-finite solutions. A nonzero _P^~_E-function is called _P^~_E-minimal if it is a constant multiple of every nonzero _P^~_E-function dominated by it. THEOREM. There exists a _P^~_E-minimal function if and only if there exists a point in q ϵ Γ such that m^P(q) > 0. THEOREM. For q ϵ Δ^P , m^P(q) > 0 if and only if m⁰(q) > 0 .