During development, multipotent stem cells divide and respond to cues that lead to their terminal differentiation. Isshiki et al. studied the Drosophila nervous system to learn about the sequence of transcription factors responsible for determining cell fate in lineages from specific neural precursors. In Drosophila, the multipotent neuroblasts divide asymmetrically to produce a cell that will differentiate [these cells will become ganglion mother cells (GMCs)] and a cell that retains multipotency. Isshiki et al. identified an invariant linear pattern of expression of four transcription factors [hunchback (hb), Krüppel (Kr), pdm, and castor (cas)] that are sequentially expressed transiently in most neuroblast precursors and that persist in the differentiating GMCs. Thus, hb is expressed in the earliest born GMCs and is required for their differentiation, and Kr is expressed in the second-born GMCs and is required for their differentiation. One surprising result was that hb mutants lacked only the GMC-1 cells and the Kr mutants lacked only the GMC-2 cells. This suggests that these transcription factors act independently of one another in terms of the history of the cell. Persistent expression of either hb or Kr resulted in increased numbers of their respective GMCs at the expense of later GMCs, suggesting a conversion of later GMC phenotypes to earlier ones. Although the later neuroblasts can differentiate in the absence of the first transcription factors, the later neuroblasts do not differentiate properly if the first transcription factors persist in the multipotent precursor daughter cell, indicating that there is a regulatory interaction among these proteins.
T. Isshiki, B. Pearson, S. Holbrook, C. Q Doe, Drosophila neuroblasts sequentially express transcription factors which specify the temporal identity of their neuronal progeny. Cell 106, 511-521 (2001). [Online Journal]