Understanding how differentiation is maintained: lessons from the Drosophila brain

Abstract

The ability to maintain cells in a differentiated state and to prevent them from reprogramming into a multipotent state has recently emerged as a central theme in neural development as well as in oncogenesis. In the developing central nervous system (CNS) of the fruit fly Drosophila, several transcription factors were recently identified to be required in postmitotic cells to maintain differentiation, and in their absence, mature neurons undergo dedifferentiation, giving rise to proliferative neural stem cells and ultimately to tumor growth. In this review, we will highlight the current understanding of dedifferentiation and cell plasticity in the Drosophila CNS.

Keywords: Dedifferentiation; Neural stem cells; Neuroblast; Neurons; Post-mitotic cells.

Fig. 1

Dedifferentiation in the Drosophila brain. a Wild-type neuroblasts (NBs) divide asymmetrically to self-renew and to generate a smaller daughter cell, the ganglion mother cell (GMC) that divide once to generate differentiated neurons. b pros mutant GMCs are unable to differentiate and re-acquire a NB fate [6]. c mdlc mutant neurons express NB markers but are unable to proliferate [20]. d lolaN mutant post-mitotic neurons in the optic lobes dedifferentiate and re-enter the cell cycle [34]. e Nerfin-1-deficient post-mitotic neurons dedifferentiate, re-enter the cell cycle and grow back to give rise to a fully functional NB [32]