Cis-Regulatory Mechanisms for Robust Olfactory Sensory Neuron Class-restricted Odorant Receptor Gene Expression in Drosophila

Abstract

Odor perception requires that each olfactory sensory neuron (OSN) class continuously express a single odorant receptor (OR) regardless of changes in the environment. However, little is known about the control of the robust, class-specific OR expression involved. Here, we investigate the cis-regulatory mechanisms and components that generate robust and OSN class-specific OR expression in Drosophila. Our results demonstrate that the spatial restriction of expression to a single OSN class is directed by clusters of transcription-factor DNA binding motifs. Our dissection of motif clusters of differing complexity demonstrates that structural components such as motif overlap and motif order integrate transcription factor combinations and chromatin status to form a spatially restricted pattern. We further demonstrate that changes in metabolism or temperature perturb the function of complex clusters. We show that the cooperative regulation between motifs around and within the cluster generates robust, class-specific OR expression.

Sensory neuron lineage mapping and manipulation in theDrosophila olfactorysystem

“…Recent advances in genome-editing and single-cell RNA-seq or chromatin profiling technologies have been revolutionary for documenting and classifying cell-type diversity in the nervous system (and other tissues), as well as in defining their lineage relationships (e.g., (Raj et al, 2018;Zhong et al, 2018)). With our OSN lineage driver, we may now exploit such technologies to examine the gene expression and epigenetic states of the at1 lineage from birth to maturity, and how these may be influenced by internal state and environmental conditions, both of which have been shown to impact OSN specification (Jafari and Alenius, 2015). While cellular-resolution level transcriptomic/epigenomic data is undeniably important to understand neural development, the combination of these with tools for visualization of specific lineages in vivo is essential for a complete view of how structural and functional diversity develops in the nervous system.…”

Identification of a molecular basis for the juvenile sleep state

“…How does pdm3 coordinate appropriate DA innervation of the dFSB at the molecular level? Pdm3 binds to a TAAT Hox motif 2-3 base pairs upstream of a POU motif (TGCAA/T) (Andersen and Rosenfeld, 2001;Jafari and Alenius, 2015). Transcriptional targets of pdm3 remain largely uncharacterized (Jafari and Alenius, 2015;Tichy et al, 2008).…”

“…Pdm3 binds to a TAAT Hox motif 2-3 base pairs upstream of a POU motif (TGCAA/T) (Andersen and Rosenfeld, 2001;Jafari and Alenius, 2015). Transcriptional targets of pdm3 remain largely uncharacterized (Jafari and Alenius, 2015;Tichy et al, 2008). To determine which genes affect sleep ontogeny downstream of pdm3, we performed RNA-Seq analysis of central brains in pdm3 knockdown and controls at the mid-pupal stage (Fig 8A, n = 4…”

Pdm3 directs sleep circuit development to control sleep maturation

“…How does pdm3 coordinate appropriate DA innervation of the dFSB at the molecular 265 level? Pdm3 binds to a TAAT Hox motif 2-3 base pairs upstream of a POU motif (TGCAA/T) (Andersen and Rosenfeld, 2001;Jafari and Alenius, 2015). Transcriptional targets of pdm3 remain largely uncharacterized (Jafari and Alenius, 2015;Tichy et al, 2008).…”

“…Pdm3 binds to a TAAT Hox motif 2-3 base pairs upstream of a POU motif (TGCAA/T) (Andersen and Rosenfeld, 2001;Jafari and Alenius, 2015). Transcriptional targets of pdm3 remain largely uncharacterized (Jafari and Alenius, 2015;Tichy et al, 2008). To determine which genes affect sleep ontogeny downstream of pdm3, we performed RNA-Seq analysis of central brains in pdm3 knockdown and controls at the Fig S6).…”