Abstract
Left-right laterality is an important aspect of human –and in fact all vertebrate– brain organization for which the genetic basis is poorly understood. Using RNA sequencing data we contrasted gene expression in left- and right-sided samples from several structures of the anterior central nervous systems of post mortem human embryos and foetuses. While few individual genes stood out as significantly lateralized, most structures showed evidence of laterality of their overall transcriptomic profiles. These left-right differences showed overlap with age-dependent changes in expression, indicating lateralized maturation rates, but not consistently in left-right orientation over all structures. Brain asymmetry may therefore originate in multiple locations, or if there is a single origin, it is earlier than 5 weeks post conception, with structure-specific lateralized processes already underway by this age. This pattern is broadly consistent with the weak correlations reported between various aspects of adult brain laterality, such as language dominance and handedness.
Highlights
Like other vertebrate brains[1], the human brain shows left-right laterality of its anatomy and function[1,2,3,4,5,6,7,8]
We showed that the spinal cords and hindbrains of human embryos aged in the range of 4 to 8 pcw showed left-right differences in gene expression that were related to a difference in maturation rates of the two sides[22]
In terms of individual genes, we found KCTD12 and SNAI1 to be asymmetrically expressed towards the right in the 5–5.5pcw forebrain after false discovery rate correction, as well as targets of the transcription factor FOXJ1
Summary
Like other vertebrate brains[1], the human brain shows left-right laterality of its anatomy and function[1,2,3,4,5,6,7,8]. In order to assess transcriptomic laterality in anterior CNS regions at earlier stages than previously studied, here we generated a new RNA sequencing dataset based on the left and right forebrains and midbrains of human embryos aged 5–5.5pcw, for which healthy pregnancies had been terminated by voluntary medical abortions. The Human Developmental Biology Resource (UK) recently released a transcriptomic dataset in which various structures of the developing brain, in the age range 7.5–14pcw, had been separated into left and right prior to RNA sequencing[26], which included cerebral cortex separated into temporal and non-temporal lobe, basal ganglion, diencephalon, and choroid plexus of the lateral ventricles. A third publicly available dataset from embryos aged 4.5–9pcw included various structures which had not been separated into left and right[26], but was useful in assessing age-dependent changes of gene expression spanning the range of 5–5.5pcw
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