Sylvian fissure development is linked to differential genetic expression in the pre-folded brain

Arka N Mallela,Hansen Deng,Alyssa K Brisbin,Alan Bush,Ezequiel Goldschmidt

doi:10.1038/s41598-020-71535-4

Abstract

The mechanisms by which the human cerebral cortex folds into its final form remain poorly understood. With most of the current models and evidence addressing secondary folds, we sought to focus on the global geometry of the mature brain by studying its most distinctive feature, the Sylvian fissure. A digital human fetal brain atlas was developed using previously obtained MRI imaging of 81 healthy fetuses between gestational ages 21 and 38 weeks. To account for the development of the Sylvian fissure, we compared the growth of the frontotemporal opercula over the insular cortex and compared the transcriptome of the developing cortices for both regions. Spatiotemporal mapping of the lateral hemispheric surface showed the highest rate of organized growth in regions bordering the Sylvian fissure of the frontal, parietal and temporal lobes. Volumetric changes were first observed in the posterior aspect of the fissure moving anteriorly to the frontal lobe and laterally in the direction of the temporal pole. The insular region, delineated by the limiting insular gyri, expanded to a much lesser degree. The gene expression profile, before folding begins in the maturing brain, was significantly different in the developing opercular cortex compared to the insula. The Sylvian fissure forms by the relative overgrowth of the frontal and temporal lobes over the insula, corresponding to domains of highly expressed transcription factors involved in neuroepithelial cell differentiation.

Highlights

The mechanisms by which the human cerebral cortex folds into its final form remain poorly understood
Our goal is to evaluate the development of the Sylvian fissure as a result of asymmetric cortical growth between the frontoparietal and temporal opercula with respect to the insular cortex
Our analysis demonstrates that focal areas of cortical growth and convergent growth of the opercula close the Sylvian fissure

Summary

Introduction

The mechanisms by which the human cerebral cortex folds into its final form remain poorly understood. A number of hypotheses have been proposed on the mechanisms of preterm brain folding11,12 These include mechanical instability that can arise from the outer gray matter expanding at a faster rate than the underlying white matter, the axonal tension hypothesis in which white matter axons draw together overlying cortical regions to form gyri, and genetic prepatterning of the cortex to form c onvolutions. Abnormal morphologic features of the Sylvian fissure can be frequently associated with neuronal migration d isorders22,23 The development of this prominent fold defines the global shape of the brain and cannot be explained by current models, which render aleatory sulci and gyri, with no distinctive and reproducible large scale structure. Our hypothesis is that the convergence of the frontal and temporal opercula over the insula, driven by discrete regions of high growth, are responsible for the formation of the fissure and are associated with differential genetic expression patterns

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