Abstract
BackgroundNervous systems are generally bilaterally symmetric on a gross structural and organizational level but are strongly lateralized (left/right asymmetric) on a functional level. It has been previously noted that in vertebrate nervous systems, symmetrically positioned, bilateral groups of neurons in functionally lateralized brain regions differ in the size of their soma. The genetic mechanisms that control these left/right asymmetric soma size differences are unknown. The nematode Caenorhabditis elegans offers the opportunity to study this question with single neuron resolution. A pair of chemosensory neurons (ASEL and ASER), which are bilaterally symmetric on several levels (projections, synaptic connectivity, gene expression patterns), are functionally lateralized in that they express distinct chemoreceptors and sense distinct chemosensory cues.ResultsWe describe here that ASEL and ASER also differ substantially in size (soma volume, axonal and dendritic diameter), a feature that is predicted to change the voltage conduction properties of the two sensory neurons. This difference in size is not dependent on sensory input or neuronal activity but developmentally programmed by a pathway of gene regulatory factors that also control left/right asymmetric chemoreceptor expression of the two ASE neurons. This regulatory pathway funnels via the DIE-1 Zn finger transcription factor into the left/right asymmetric distribution of nucleoli that contain the rRNA regulator Fibrillarin/FIB-1, a RNA methyltransferase implicated in the non-hereditary immune disease scleroderma, which we find to be essential to establish the size differences between ASEL and ASER.ConclusionsTaken together, our findings reveal a remarkable conservation of the linkage of functional lateralization with size differences across phylogeny and provide the first insights into the developmentally programmed regulatory mechanisms that control neuron size lateralities.
Highlights
Nervous systems are generally bilaterally symmetric on a gross structural and organizational level but are strongly lateralized on a functional level
The pair of ASE neurons displays size asymmetries We visualized the ASEL and ASER gustatory neurons in live animals using chromosomally integrated gfp reporter gene constructs in which ASE-expressed cis-regulatory sequences drive non-localized green fluorescent protein (GFP), which diffuses throughout the entire cell and its processes (Figure 1A)
Using two different transgenes, we find that the two neuron soma show consistent and highly stereotyped size differences in adult animals
Summary
Nervous systems are generally bilaterally symmetric on a gross structural and organizational level but are strongly lateralized (left/right asymmetric) on a functional level. It has been previously noted that in vertebrate nervous systems, symmetrically positioned, bilateral groups of neurons in functionally lateralized brain regions differ in the size of their soma. The genetic mechanisms that control these left/right asymmetric soma size differences are unknown. Signaling pathways triggered by insulin and TGFb are known to control In spite of these advances, size regulation in the nervous system is poorly understood, even though the size differences of neurons are astonishing. Caenorhabditis elegans and Ascaris suum have the same number and types of neurons (their axonal projection patterns are identical as well), yet they differ in soma size and neuronal processes length by several orders of magnitude [7]. The importance of the PTEN-mediated neuron-size regulation is illustrated by Lhermitte-Duclos disease, which is characterized by overgrowth of neuronal soma [8,9]
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