Fork(head) in the path required for convergent differentiation

Convergent differentiation refers to the phenomenon by which identical or highly similar cells are produced from multiple lineages. This developmental process has long been documented in Caenorhabditis elegans and now, thanks to technical advances in single cell sequencing and lineage tracing, is also recognised in vertebrates. In this issue, Karolina Mizeracka and colleagues use C. elegans to identify one of the elusive transcription factors involved in this lineage-specific cell type specification. Their model of choice is the inner labial socket (ILso) glia, which include dorsal, lateral and ventral pairs of cells. The authors screen for mutations affecting a single pair of ILso glia, while the other pairs remain unaffected. They identify that UNC-130, the C. elegans Forkhead transcription factor, is required for the proper specification of the dorsal pair only. They find that UNC-130 is highly expressed in the progenitor of the dorsal ILso glia when the cells are born and the expression level declines as these cells differentiate. Rescue experiments reveal that UNC-130 acts as a transient transcriptional repressor, and can be functionally replaced by its vertebrate homolog, FoxD3. Together these results highlight UNC-130/FoxD3 as lineage-specific regulatory factors that may represent an evolutionarily conserved mechanism for convergent differentiation.