TY - JOUR TI - A transient role of the ciliary gene Inpp5e in controlling direct versus indirect neurogenesis in cortical development AU - Hasenpusch-Theil, Kerstin AU - Laclef, Christine AU - Colligan, Matt AU - Fitzgerald, Eamon AU - Howe, Katherine AU - Carroll, Emily AU - Abrams, Shaun R AU - Reiter, Jeremy F AU - Schneider-Maunoury, Sylvie AU - Theil, Thomas A2 - Tissir, Fadel A2 - Bronner, Marianne E A2 - Tissir, Fadel VL - 9 PY - 2020 DA - 2020/08/25 SP - e58162 C1 - eLife 2020;9:e58162 DO - 10.7554/eLife.58162 UR - https://doi.org/10.7554/eLife.58162 AB - During the development of the cerebral cortex, neurons are generated directly from radial glial cells or indirectly via basal progenitors. The balance between these division modes determines the number and types of neurons formed in the cortex thereby affecting cortical functioning. Here, we investigate the role of primary cilia in controlling the decision between forming neurons directly or indirectly. We show that a mutation in the ciliary gene Inpp5e leads to a transient increase in direct neurogenesis and subsequently to an overproduction of layer V neurons in newborn mice. Loss of Inpp5e also affects ciliary structure coinciding with reduced Gli3 repressor levels. Genetically restoring Gli3 repressor rescues the decreased indirect neurogenesis in Inpp5e mutants. Overall, our analyses reveal how primary cilia determine neuronal subtype composition of the cortex by controlling direct versus indirect neurogenesis. These findings have implications for understanding cortical malformations in ciliopathies with INPP5E mutations. KW - Inpp5e KW - Gli3 KW - primary cilium KW - neurogenesis KW - cortex JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -