New insights in the clockwork mechanism regulating lineage specification: Lessons from the Drosophila nervous system

Powerful transcription factors called fate determinants induce robust differentiation programs in multipotent cells and trigger lineage specification. These factors guarantee the differentiation of specific tissues/organs/cells at the right place and the right moment to form a fully functional organism. Fate determinants are activated by temporal, positional, epigenetic, and post-transcriptional cues, hence integrating complex and dynamic developmental networks. In turn, they activate specific transcriptional/epigenetic programs that secure novel molecular landscapes.

In this review, we use the Drosophila Gcm glial determinant as a model to discuss the mechanisms that allow lineage specification in the nervous system. The dynamic regulation of Gcm via interlocked loops has recently emerged as a key event in the establishment of stable identity. Gcm induces gliogenesis while triggering its own extinction, thus preventing the appearance of metastable states and neoplastic processes.

Using simple animal models that allow in vivo manipulations provides a key tool to disentangle the complex regulation of cell fate determinants.