Neurog1andNeurog2Control Two Waves of Neuronal Differentiation in the Piriform Cortex

• DOI: 10.1523/jneurosci.0614-13.2014
• Publication Date: 2014-01-08T17:54:10Z
• Authors: Rajiv Dixit; Grey Wilkinson; Gonzalo I. Cancino; Tarek Shaker; Lata Adnani; Saiqun Li; Daniel Dennis; Deborah Kurrasch; Jennifer A. Chan; Eric C. Olson; David R. Kaplan; Céline Zimmer; Carol Schuurmans
• Keywords: Cerebral Cortex; Male; Neurons; 0301 basic medicine; 2. Zero hunger; 0303 health sciences; Neurogenesis; Cell Differentiation; Nerve Tissue Proteins; Embryo, Mammalian; Immunohistochemistry; Mice, Mutant Strains; Mice; 03 medical and health sciences; Electroporation; Neural Stem Cells; Basic Helix-Loop-Helix Transcription Factors; Animals; Female; In Situ Hybridization

The three-layered piriform cortex, an integral part of the olfactory system, processes odor information relayed by olfactory bulb mitral cells. Specifically, mitral cell axons form the lateral olfactory tract (LOT) by targeting lateral olfactory tract (lot) guidepost cells in the piriform cortex. While lot cells and other piriform cortical neurons share a pallial origin, the factors that specify their precise phenotypes are poorly understood. Here we show that in mouse, the proneural genesNeurog1andNeurog2are coexpressed in the ventral pallium, a progenitor pool that first gives rise to Cajal-Retzius (CR) cells, which populate layer I of all cortical domains, and later to layer II/III neurons of the piriform cortex. Using loss-of-function and gain-of-function approaches, we find thatNeurog1has a unique early role in reducing CR cell neurogenesis by temperingNeurog2's proneural activity. In addition,Neurog1andNeurog2have redundant functions in the ventral pallium, acting in two phases to first specify a CR cell fate and later to specify layer II/III piriform cortex neuronal identities. In the early phase,Neurog1andNeurog2are also required for lot cell differentiation, which we reveal are a subset of CR neurons, the loss of which prevents mitral cell axon innervation and LOT formation. Consequently, mutation ofTrp73, a CR-specific cortical gene, results in lot cell and LOT axon displacement.Neurog1andNeurog2thus have unique and redundant functions in the piriform cortex, controlling the timing of differentiation of early-born CR/lot cells and specifying the identities of later-born layer II/III neurons.