MAPPING GRADIENTS OF NEUROGENESIS ACROSS THE FOETAL HUMAN CORTEX

The diverse regional properties of the adult cortex arise from a sequence of developmental events whose orderly progression and mutual interactions gradually shape cortical organization. Among these, neurogenesis represents the earliest process required for building the prospective cortex. Although neurogenic rates are known to vary across cortical regions, a systematic characterisation of their spatial gradients is missing. Here, we leveraged the Boyd collection - an extensive archival collection of human foetal histological material, covering the period of 11 to 18 post-gestational weeks, to comprehensively characterise neurogenesis gradients across the early developing human cortex. We measured cortical plate thickness across serial histological sections in 15 foetal human brains to derive neurogenesis maps spanning the full extent of the cortical surface. Our results conclusively demonstrate a lack of the previously proposed anterior-posterior gradient in neurogenesis across the human foetal cortex. Rather, neurogenesis was most advanced along the lateral cortical surface and progressed along ventral–dorsal and core–periphery lateral gradients. Each cortical surface also displayed distinct, surface-specific patterns: the superior surface showed an anterior–posterior gradient in neurogenesis rate, whereas no consistent gradient was found on the inferior surface. In contrast, both the anterior and posterior cortical surfaces demonstrated U-shaped gradients characterised by a more advanced neurogenesis at dorsal and ventral extremes and a relative delay towards the polar regions. This work provides a spatial characterisation of neurogenesis gradients across the early foetal human cortex and presents a step forward in our fundamental understanding of this core developmental process.