G2-phase arrest prevents bristle progenitor self-renewal and synchronizes cell divisions with cell fate differentiation

Abstract

Developmentally regulated cell cycle arrest is a fundamental feature of neurogenesis, whose significance is poorly understood. During Drosophila sensory organ (SO) development, primary progenitor (pI) cells arrest in G2-phase for precisely defined periods. Upon re-entering the cell cycle in response to developmental signals, these G2-arrested precursor cells divide and generate specialized neuronal and non-neuronal cells. To study how G2-phase arrest affects SO lineage specification, we forced pI-cells to divide prematurely. This produced SO with normal neuronal lineages but supernumerary non-neuronal cell types. The reason was that prematurely dividing pI-cells generated a secondary pI-cell that produced a complete SO and an external precursor cell that underwent amplification divisions producing supernumerary non-neural cells. This means that pI-cells are capable to undergo self-renewal before transit to a terminal mode of division. Regulation of G2-phase arrest therefore serves a dual role in SO development: preventing progenitor self-renewal and synchronizing cell division with developmental signals. Cell cycle arrest in G2-phase therefore temporally coordinates the precursor cells proliferation potential with terminal cell fate determination to ensure formation of organs with a normal set of sensory cells.