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

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. The human cerebral cortex at birth has completed the formation of all major gyral and sulcal folds. The cerebral surface grows from a largely smooth surface beginning at the sixth month of gestation to the characteristic patterns of gyrification 1-10. A number of hypotheses have been proposed on the mechanisms of preterm brain folding 11,12. 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 convolutions 2,3,13,14. Postnatally, cortical expansion continues through differential local growth that extend into adulthood, without altering the newborn's brain folded outline 15. With most of the current evidence focusing on the formation of intralobar folds, how the brain acquires its final global form is largely unknown, including the development of its most distinctive feature, the formation of the Sylvian fissure 2,3,5,13,16-18. Observations of cortical development in preterm infants have shown that maximal directional growth occurs from the central sulcus toward the parietal lobe, then toward the frontal and temporal regions 19,20. The normal process of cortical development follows a predictable sequence 21. The Sylvian fissure, the deepest sulcus on the lateral hemispheric surface, can be identified as early as 12 weeks of gestation and serves as a major landmark for the dynamic changes of the brain surfac...

Brain folding shapes the branching pattern of the middle cerebral artery

“…Brain folding occurs in different dimensions. The development of the sulci and gyri within a lobe is the result from biological and physical phenomena, ultimately bending the brain surface by tangential expansion; the folding of the frontal and temporal lobe over the insula, to form the Sylvian fissure, is a completely different event [ 19 ]. Bush et al previously suggested that the Sylvian fissure appears by convergence of the anterior and posterior poles of the embryonic telencephalon and proposed a convergence index for the adult brain, calculated as the Euclidean distance/transcortical distance ratio, that returns its highest values around the fissure [ 20 ].…”

“…https://doi.org/10.1371/journal.pone.0245167.g003 form the Sylvian fissure, is a completely different event [19]. Bush et al previously suggested that the Sylvian fissure appears by convergence of the anterior and posterior poles of the embryonic telencephalon and proposed a convergence index for the adult brain, calculated as the Euclidean distance/transcortical distance ratio, that returns its highest values around the fissure [20].…”

Cadaveric White Matter Dissection Study of the Telencephalic Flexure: Surgical Implications

“…Since 13 gw, cells from the subpallial neurons migrate into the insular cortex along the radial glial fascicle reaching the final configuration before birth ( 16 ). Mallela et al ( 17 , 18 ) found different gene expressions from the opercula to the insula resulting in the highest proliferation of the former allowing their growth over the insula. This different origin might explain the fact that the tracts that developed later connecting frontal, temporal, and parietooccipital regions ‘avoid crossing the insula', thus being located ventral or dorsal to it, and in some cases wrapping around it with specific curved patterns ( 19 – 21 ).…”

“…Since 13 gw, cells from the subpallial neurons migrate into the insular cortex along the radial glial fascicle reaching the final configuration before birth (16). Mallela et al (17,18) found different gene expressions from the opercula to the insula resulting in the highest proliferation of the former allowing their growth over the insula. This different origin might explain the fact that the tracts that developed later FIGURE 8 | An 18-year-old left-handed girl presented with medically refractory epilepsy that was symptomatic since the age of 3 years due to a perinatal stroke in the territory of the left middle cerebral artery.…”

Exploring the emergence of morphological asymmetries around the brain’s Sylvian fissure: a longitudinal study of shape variability in preterm infants

“…Moreover, the gene expression profile of the pre-folded brain has been reported to be significantly different in the developing opercular cortex compared to the insular cortex (Mallela et al, 2020).…”