We study the mechanisms of neurogenesis in order to implement them for neuronal repair. I will discuss a new layer of regulation in development and repair – namely organellar heterogeneity. I will introduce the concept that common cellular organelles are much more heterogeneous, i.e. different between cell and even subtypes, than previously anticipated and that this matters for development, disease and repair.

I will first give an example how this matters for development and disease. At which organelle in the cell a protein is located helps explaining why mutations of a common protein present in all cells of our body exert a disease phenotype only in the brain, because there the respective protein has a different organellar localization as in other cell types. This explains organ-specificity of disease phenotypes of ubiquitously expressed proteins.

I will then proceed to repair approaches, namely, how to replace lost neurons – either by transplantation of new neurons or direct neuronal reprogramming from local glial cells. I will highlight how organellar heterogeneity matters for the later discussing the function of mitochondrial heterogeneity and its role in direct neuronal reprogramming including human astroglia-to neuron conversion.

Taken together, our knowledge about basic mechanisms of neurogenesis allowed making great strides towards neuronal repair.

This Heller lecture is available to watch online HERE