Ciliary control of early neuron differentiation: a key mechanism in neurodevelopmental disorders?

Cilia, antenna-like signaling organelles, emanate from the surface of most cells of the human body including brain cell types.

We have discovered a new function for cilia-based signaling and communication: to promote neuron differentiation during brain development, to “manage” the time window of transition from neural precursor to differentiated, functional neuron.Using human ciliated neuronal cell models we determine how, starting at neuron polarization, ciliary signaling through e.g. the Wnt pathway is critically important for axon outgrowth and arborization; prerequisites for subsequent neuronal connectivity in the brain.

With (live cell) imaging, genetic perturbation and transcriptomics we derive mechanistic insight into how cilia-directed signal transduction translates intracellularly into anatomical changes.

Ciliary signaling is an ideal communication lever between cell-intrinsic developmental programs and cell-extrinsic influences (the immediate environment of a newborn neuron in time and space) before neurons develop synapses as their main communication tools.We anticipate that our work in neurons will serve as a template for other (human) ciliated cell types that also undergo final, functional differentiation from precursor to terminal cell type.

We will also improve the understanding of human neurodevelopmental disorders (NDDs), where (suspected) cilia malfunction early on may result in impaired neurons, which then contribute to NDD-associated brain malfunctions.