Be there or be square. In the double cortex pathology, neurons fail to migrate in proper layer and are stuck at the far back of cortex in a band below layer 6. These won’t get to see or hear much of the cortical play owing to their position and to defects in dendritogenesis and synaptogenesis. Interestingly, the same gene mutation introduced in neurons correctly positioned has milder consequences suggesting that laminar fate and full neuronal differenciation are linked, as in a VIP package. (I. Bureau)
Scientific abstract: The neocortex is a 6-layered laminated structure with a precise anatomical and functional organization ensuring proper function. Laminar positioning of cortical neurons, as determined by termination of neuronal migration, is a key determinant of their ability to assemble into functional circuits. However, the exact contribution of laminar placement to dendrite morphogenesis and synapse formation remains unclear. Here we manipulated the laminar position of cortical neurons by knocking down doublecortin (Dcx), a crucial effector of migration, and show that misplaced neurons fail to properly form dendrites, spines, and functional glutamatergic and GABAergic synapses. We further show that knocking down Dcx in properly positioned neurons induces similar but milder defects, suggesting that the laminar misplacement is the primary cause of altered neuronal development. Thus, the specific laminar environment of their fated layers is crucial for the maturation of cortical neurons, and influences their functional integration into developing cortical circuits.