Time course of ferret brain morphogenesis.

a, Whole brain samples from ferrets of various ages show progressive development of cortical gyri and sulci. b, Ferret brains show an increase in complexity of sulcal pattern and in sulcal depth throughout development. The rhinal sulcus (rs), cruciate sulcus (crs), coronal sulcus (cns), suprasylvian sulcus (sss), pseudosylvian sulcus (pss), lateral sulcus (ls), and ansate sulcus (as) are labelled. Schematic by G. Séjourné.

Physical gel model of ferret brain morphogenesis.

a, Schematic of the gel experiment. We first produced a two-layer gel model of a ferret brain from MRI scans as previously described (17). We then immersed the gel model in n-hexane for 1.5 hours, which induced the outer layer to swell by absorbing the solvent over time, resulting in the development of cortical gyri and sulci. b, The swelling experiment for the P8 ferret model, in which it can be observed that the swelling of the cortical layer produces sulcal patterns and characteristics comparable to the real ferret brain. c, The swelling experiment for the P16 gel model. Scale bar = 1cm. Notation guide: cruciate sulcus (crs), coronal sulcus (cns), suprasylvian sulcus (sss), rhinal sulcus (rs), pseudosylvian sulcus (pss), lateral sulcus (ls), ansate sulcus (as).

Numerical model of ferret brain morphogenesis.

a, Continuous growth simulation from P0 to adolescence. The P0 brain tetrahedral mesh was used as the input for the numerical simulation. b, Stepwise growth simulation from P0 to P4, P4 to P8, P8 to P16, and P16 to P32. For different growth intervals, we use different brain tetrahedral meshes as the input for the numerical simulation. Different views of the input P0 brain and the simulated P16 brain are provided.

Comparison of cortical folding in real and simulated ferret brain models.

a, The top row shows the increase in complexity of sulcal pattern and in sulcal depth of ferret brains from P8 to P16. The middle row shows a numerical model of a P8 brain and its deformed state mimicking progression to P16. The bottom row shows a physical gel model of P8 and its post-swelling state mimicking progression to P16 (scale bar = 1cm). The P8 initial states have invaginations corresponding to the cruciate sulcus (crs), coronal sulcus (cns) and suprasylvian sulcus (sss), and both the numerical deformed state and the physical post-swelling state have sulci corresponding in location and self-contacting nature to the crs, cns, sss, lateral sulcus (ls), and ansate sulcus (as) observed in P16 real ferrets. b, The real P16 brain reconstructed from MRI scans, the simulated P16 brain, and their respective landmark-aligned spherical mappings obtained by the FLASH algorithm (37), each color-coded with the shape index (38) of the brain.

Modeling malformations of cortical development (MCD) using our model.

a, Control. b, SCN3A. c, ASPM. d, TMEM161B. For each example, we show human (top) and ferret (middle) brain MRIs. We then perform a modified numerical brain simulation on the P8 model with different tangential growth rate and cortical thickness parameters, including (a) the original growth rate and cortical thickness, (b) a reduction of the cortical thickness at a localized zone, (c) a reduction of the growth rate globally, and (d) a reduction of the growth rate and an increase of the cortical thickness globally. All numerical simulation results (bottom) qualitatively capture the cortical malformations.