Developmental control of lateralized neuron size in the nematode Caenorhabditis elegans

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.

The Small GTPase Rheb Affects Central Brain Neuronal Morphology and Memory Formation in Drosophila

“…In flies, both Rheb overexpression and Tsc1 null clones induce a similar enlarged cell phenotype [6], [7], [10], [21]. Additionally, neuronal cell body size increases due to Rheb overexpression have also been seen in another invertebrate, C. elegans [47]. The increase that we observe in Kenyon cell body size with Rheb overexpression is in line with the growth phenotypes seen in these prior studies.…”

The TGF-β Family inCaenorhabditis elegans

“…Mutants in Sma/Mab pathway components have the same number of nuclei as wild-type, indicating that some cells must be reduced in size rather than in number (Nagamatsu and Ohshima 2004). The cell size reduction is not universal, however, because the neuronal soma size is not altered (Goldsmith et al 2010). …”

TGF-β signaling in C. elegans

“…The degree of reduction in the size of hypodermal (epidermal) seam cells and the large hypodermal syncytium hyp7 is most proportional to the degree of reduction in body size (Nagamatsu and Ohshima, 2004; Nyström et al, 2002; Wang et al, 2002). In contrast, neuronal soma size is not modulated by the DBL-1 pathway (Goldsmith et al, 2010). Studies directing expression of the receptors and Smads to particular tissues have demonstrated that the hypodermis, but not the intestine, plays a major role in regulation of body size (Inoue and Thomas, 2000a; Schulenburg et al, 2004; Wang et al, 2002; Yoshida et al, 2001).…”