Atlas-builder software and the eNeuro atlas: resources for developmental biology and neuroscience

Abstract

A major limitation in understanding embryonic development is the lack of cell type-specific markers. Existing gene expression and marker atlases provide valuable tools, but they typically have one or more limitations: a lack of single-cell resolution; an inability to register multiple expression patterns to determine their precise relationship; an inability to be upgraded by users; an inability to compare novel patterns with the database patterns; and a lack of three-dimensional images. Here, we develop new 'atlas-builder' software that overcomes each of these limitations. A newly generated atlas is three-dimensional, allows the precise registration of an infinite number of cell type-specific markers, is searchable and is openended. Our software can be used to create an atlas of any tissue in any organism that contains stereotyped cell positions. We used the software to generate an 'eNeuro' atlas of the Drosophila embryonic CNS containing eight transcription factors that mark the major CNS cell types (motor neurons, glia, neurosecretory cells and interneurons). We found neuronal, but not glial, nuclei occupied stereotyped locations. We added 75 new Gal4 markers to the atlas to identify over 50% of all interneurons in the ventral CNS, and these lines allowed functional access to those interneurons for the first time. We expect the atlas-builder software to benefit a large proportion of the developmental biology community, and the eNeuro atlas to serve as a publicly accessible hub for integrating neuronal attributes -cell lineage, gene expression patterns, axon/dendrite projections, neurotransmitters -and linking them to individual neurons.

Whole-organism cellular gene-expression atlas reveals conserved cell types in the ventral nerve cord of Platynereis dumerilii

“…At this stage, the nervous system and locomotor apparatus is largely differentiated and fully functional. So far, in other animal models similar cellular resolution expression atlases exist for selected tissues only (29,30). Building on previous image registration approaches (25,26), ProSPr is a highly automated and easy-to-customize technique, running in free license software (Scripts available in prospr.embl.…”

Even-Skipped+ Interneurons Are Core Components of a Sensorimotor Circuit that Maintains Left-Right Symmetric Muscle Contraction Amplitude

“…The segmented larva has ~30 bilateral body wall muscles per segment and a similar number of motor neurons, and their role during larval locomotion has been characterized (Berni et al, 2012; Crisp et al, 2008; Crisp et al, 2011; Dixit et al, 2008; Heckscher et al, 2012; Hughes and Thomas, 2007; Lahiri et al, 2011; Pulver and Griffith, 2010; Schaefer et al, 2010). In contrast, there are ~270 bilateral interneurons per segment (Heckscher et al, 2014; Rickert et al, 2011) and their role in locomotion is almost completely unknown (Kohsaka et al, 2014). Recently, we identified several hundred Gal4 lines that express in a sparse pattern of neurons in the late embryonic CNS, and determined their expression pattern at single neuron resolution for 75 of these lines (Heckscher et al, 2014; Manning et al, 2012).…”

“…In contrast, there are ~270 bilateral interneurons per segment (Heckscher et al, 2014; Rickert et al, 2011) and their role in locomotion is almost completely unknown (Kohsaka et al, 2014). Recently, we identified several hundred Gal4 lines that express in a sparse pattern of neurons in the late embryonic CNS, and determined their expression pattern at single neuron resolution for 75 of these lines (Heckscher et al, 2014; Manning et al, 2012). We used this collection of sparsely-expressed Gal4 lines to express the warmth-activated TRPA1 cation channel and screen for locomotor defects in newly hatched larvae.…”

Visualizing Whole-Brain Activity and Development at the Single-Cell Level Using Light-Sheet Microscopy

“…Such efforts introduce complementary computational challenges, e.g., the creation, integration, and comparison of static atlases of gene expression and cell-type-specific markers for the nervous system. To this end, Heckscher et al (2014) recently introduced software that addresses the general problem of building an atlas of tissues that contain cell populations in stereotyped arrangements (Figures 6E-6G). By using the transcription factor Even-skipped as a reference marker, Heckscher et al combined expression patterns from 75 Gal4 lines for the CNS of stage 16 Drosophila embryos.…”

“…Perfect prediction accuracy is indicated by a probability of 1 along the diagonal. (E) Image segmentation using the atlas building pipeline by Heckscher et al (2014). The image to the left shows a 3D rendering of a stage 16 CNS stained with antiEven-skipped (Eve).…”