Abstract
BackgroundNeurons are one of the most structurally and functionally diverse cell types found in nature, owing in large part to their unique class specific dendritic architectures. Dendrites, being highly specialized in receiving and processing neuronal signals, play a key role in the formation of functional neural circuits. Hence, in order to understand the emergence and assembly of a complex nervous system, it is critical to understand the molecular mechanisms that direct class specific dendritogenesis.Methodology/Principal FindingsWe have used the Drosophila dendritic arborization (da) neurons to gain systems-level insight into dendritogenesis by a comparative study of the morphologically distinct Class-I (C-I) and Class-IV (C-IV) da neurons. We have used a combination of cell-type specific transcriptional expression profiling coupled to a targeted and systematic in vivo RNAi functional validation screen. Our comparative transcriptomic analyses have revealed a large number of differentially enriched/depleted gene-sets between C-I and C-IV neurons, including a broad range of molecular factors and biological processes such as proteolytic and metabolic pathways. Further, using this data, we have identified and validated the role of 37 transcription factors in regulating class specific dendrite development using in vivo class-specific RNAi knockdowns followed by rigorous and quantitative neurometric analysis.Conclusions/SignificanceThis study reports the first global gene-expression profiles from purified Drosophila C-I and C-IV da neurons. We also report the first large-scale semi-automated reconstruction of over 4,900 da neurons, which were used to quantitatively validate the RNAi screen phenotypes. Overall, these analyses shed global and unbiased novel insights into the molecular differences that underlie the morphological diversity of distinct neuronal cell-types. Furthermore, our class-specific gene expression datasets should prove a valuable community resource in guiding further investigations designed to explore the molecular mechanisms underlying class specific neuronal patterning.
Highlights
A complex nervous system consists of a vast number of neuronal classes, each displaying distinctive dendritic architecture
In order to further understand the molecular differences between class I (C-I) and class IV (C-IV) neurons, we investigated gene-sets that were inversely regulated between these two classes
To serve the dual purpose of validating our microarray data and identifying candidate molecules regulating class-specific dendrite development, we focused on the identification of transcription factors (TFs) that were uniquely or commonly enriched in C-I and/ or C-IV neurons compared to the whole-larval controls
Summary
A complex nervous system consists of a vast number of neuronal classes, each displaying distinctive dendritic architecture. Dendritic branching pattern represents a hallmark of each neuronal type, and plays a functional role in signal-processing, neuronal function and circuit assembly [1]. The da neurons consist of 4 distinct morphological and functional classes (C-I-IV) of sensory neurons that have varying degrees of dendritic complexity [7]. Neurons are one of the most structurally and functionally diverse cell types found in nature, owing in large part to their unique class specific dendritic architectures. Dendrites, being highly specialized in receiving and processing neuronal signals, play a key role in the formation of functional neural circuits. In order to understand the emergence and assembly of a complex nervous system, it is critical to understand the molecular mechanisms that direct class specific dendritogenesis
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