TY - JOUR TI - Activity-dependent death of transient Cajal-Retzius neurons is required for functional cortical wiring AU - Riva, Martina AU - Genescu, Ioana AU - Habermacher, Chloé AU - Orduz, David AU - Ledonne, Fanny AU - Rijli, Filippo M AU - López-Bendito, Guillermina AU - Coppola, Eva AU - Garel, Sonia AU - Angulo, Maria Cecilia AU - Pierani, Alessandra A2 - Mason, Carol A A2 - Bronner, Marianne E A2 - Luhmann, Heiko J VL - 8 PY - 2019 DA - 2019/12/31 SP - e50503 C1 - eLife 2019;8:e50503 DO - 10.7554/eLife.50503 UR - https://doi.org/10.7554/eLife.50503 AB - Programmed cell death and early activity contribute to the emergence of functional cortical circuits. While most neuronal populations are scaled-down by death, some subpopulations are entirely eliminated, raising the question of the importance of such demise for cortical wiring. Here, we addressed this issue by focusing on Cajal-Retzius neurons (CRs), key players in cortical development that are eliminated in postnatal mice in part via Bax-dependent apoptosis. Using Bax-conditional mutants and CR hyperpolarization, we show that the survival of electrically active subsets of CRs triggers an increase in both dendrite complexity and spine density of upper layer pyramidal neurons, leading to an excitation/inhibition imbalance. The survival of these CRs is induced by hyperpolarization, highlighting an interplay between early activity and neuronal elimination. Taken together, our study reveals a novel activity-dependent programmed cell death process required for the removal of transient immature neurons and the proper wiring of functional cortical circuits. KW - apoptosis KW - neuronal activity KW - cortical development KW - excitation/inhibition ratio KW - Cajal-Retzius neurons KW - transient JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -