The core PCP protein Prickle2 regulates axon number and AIS maturation by binding to AnkG and modulating microtubule bundling.

Core planar cell polarity (PCP) genes, which are involved in various neurodevelopmental disorders such as neural tube closure, epilepsy, and autism spectrum disorder, have poorly defined molecular signatures in neurons, mostly synapse-centric. Here, we show that the core PCP protein Prickle-like protein 2 (Prickle2) controls neuronal polarity and is a previously unidentified member of the axonal initial segment (AIS) proteome. We found that Prickle2 is present and colocalizes with AnkG480, the AIS master organizer, in the earliest stages of axonal specification and AIS formation. Furthermore, by binding to and regulating AnkG480, Prickle2 modulates its ability to bundle microtubules, a crucial mechanism for establishing neuronal polarity and AIS formation. Prickle2 depletion alters cytoskeleton organization, and Prickle2 levels determine both axon number and AIS maturation. Last, early Prickle2 depletion produces impaired action potential firing.

Developing and maintaining a nose-to-brain map of odorant identity.

Olfactory sensory neurons (OSNs) in the olfactory epithelium of the nose transduce chemical odorant stimuli into electrical signals. These signals are then sent to the OSNs' target structure in the brain, the main olfactory bulb (OB), which performs the initial stages of sensory processing in olfaction. The projection of OSNs to the OB is highly organized in a chemospatial map, whereby axon terminals from OSNs expressing the same odorant receptor (OR) coalesce into individual spherical structures known as glomeruli. This nose-to-brain map of odorant identity is built from late embryonic development to early postnatal life, through a complex combination of genetically encoded, OR-dependent and activity-dependent mechanisms. It must then be actively maintained throughout adulthood as OSNs experience turnover due to external insult and ongoing neurogenesis. Our review describes and discusses these two distinct and crucial processes in olfaction, focusing on the known mechanisms that first establish and then maintain chemospatial order in the mammalian OSN-to-OB projection.

Development of the mammalian main olfactory bulb.

The mammalian main olfactory bulb is a crucial processing centre for the sense of smell. The olfactory bulb forms early during development and is functional from birth. However, the olfactory system continues to mature and change throughout life as a target of constitutive adult neurogenesis. Our Review synthesises current knowledge of prenatal, postnatal and adult olfactory bulb development, focusing on the maturation, morphology, functions and interactions of its diverse constituent glutamatergic and GABAergic cell types. We highlight not only the great advances in the understanding of olfactory bulb development made in recent years, but also the gaps in our present knowledge that most urgently require addressing.