NDEL1 is a binding partner of LIS1 that participates in the regulation of cytoplasmic dynein function and microtubule organization during mitotic cell division and neuronal migration. NDEL1 preferentially localizes to the centrosome and is a likely target for cell cycle-activated kinases, including CDK1. In particular, NDEL1 phosphorylation by CDK1 facilitates katanin p60 recruitment to the centrosome and triggers microtubule remodeling. Here, we show that Aurora-A phosphorylates NDEL1 at Ser251 at the beginning of mitotic entry. Interestingly, NDEL1 phosphorylated by Aurora-A was rapidly downregulated thereafter by ubiquitination-mediated protein degradation. In addition, NDEL1 is required for centrosome targeting of TACC3 through the interaction with TACC3. The expression of Aurora-A phosphorylation-mimetic mutants of NDEL1 efficiently rescued the defects of centrosomal maturation and separation which are characteristic of Aurora-A-depleted cells. Our findings suggest that Aurora-A-mediated phosphorylation of NDEL1 is essential for centrosomal separation and centrosomal maturation and for mitotic entry.

The 14-3-3 proteins are a family of highly conserved, multifunctional proteins that are highly expressed in the brain during development. Cumulatively, the seven 14-3-3 isoforms make up approximately 1% of total soluble brain protein. Over the last decade, evidence has accumulated implicating the importance of the 14-3-3 protein family in the development of the nervous system, in particular cortical development, and have more recently been recognized as key regulators in a number of neurodevelopmental processes. In this review we will discuss the known roles of each 14-3-3 isoform in the development of the cortex, their relation to human neurodevelopmental disorders, as well as the challenges and questions that are left to be answered. In particular, we focus on the 14-3-3 isoforms and their involvement in the three key stages of cortical development; neurogenesis and differentiation, neuronal migration, and neuromorphogenesis and synaptogenesis.