Lineage programming: navigating through transient regulatory states via binary decisions

Abstract

Lineage-based mechanisms are widely used to generate cell type diversity in both vertebrates and invertebrates. For the past few decades, the nematode Caenorhabditis elegans has served as a primary model system to study this process because of its fixed and well-characterized cell lineage. Recent studies conducted at the level of single cells and individual cis-regulatory elements suggest a general model by which cellular diversity is generated in this organism. During its developmental history a cell passes through multiple transient regulatory states characterized by the expression of specific sets of transcription factors. The transition from one state to another is driven by a general binary decision mechanism acting at each successive division in a reiterative manner and ending up with the activation of the terminal differentiation program upon terminal division. A similar cell fate specification system seems to play a role in generating cellular diversity in the nervous system of more complex organisms such as Drosophila and vertebrates.

Figure 1

Integration of the Wnt/β-catenin asymmetric division machinery with the transcription factor cascade. Asymmetric divisions of the EMS blastomere (A), the Somatic Gonadal Precursor (B), the T blast cell (C) and the SMDD/AIY mother (D).

Figure 2

Model for the generation of cell fate diversity by reiterative use of the Wnt/β-catenin asymmetry pathway. Note that the activation of target genes by POP-1 via the repression of a repressor (REP) is hypothetical as no such repressor as been identified so far.

Figure 3

Regulation of terminal asymmetric divisions of neuronal precursors by Notch signaling. (A) Division of the MP3 precursor in the Drosophila midline. (B) Division of the p2 precursor in the vertebrate spinal cord. In red: genes activated by Notch signaling; in blue: genes repressed by Notch signaling.