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

Abstract

Background: 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.

Results: 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.

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

Keywords: cell fate determinant; feedback loop; glia.