ABSTRACT
During convergent differentiation, multiple developmental lineages produce a highly similar or identical cell type. However, the molecular players that drive convergent differentiation are not known. Here, we show that the C. elegans Forkhead transcription factor UNC-130 is required in only one of three convergent lineages that produce the same glial cell type. UNC-130 acts transiently as a repressor in progenitors and newly-born terminal cells to allow the proper specification of cells related by lineage rather than by cell type. Specification defects correlate with UNC-130:DNA binding, and UNC-130 can be functionally replaced by its human homolog, the neural crest lineage determinant FoxD3. We propose that, in contrast to terminal selectors that activate cell-type specific transcriptional programs in terminally differentiating cells, UNC-130 acts earlier to enable molecularly distinct progenitors to produce equivalent cell types. These findings provide evidence that convergent differentiation involves distinct transcriptional paths leading to the same cell type.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
1. Added analysis of unc-130 timing, including detailed lineaging of unc-130 expression in glial progenitors and functional analysis of the timing requirement using early and late promoters and timed heat-shock-induction of unc-130 in progenitors or terminal cells. 2. Added analysis of all cells in the affected lineage, including developing new markers and strains for some cells (hyp3, URB), new markers we identified for ILso (col-53, col-177), and lineage analysis of cell division patterns in unc-130 mutant embryos. 3. Added an UNC-130 DBD-Engrailed fusion that rescues almost fully in vivo, supporting the idea that UNC-130 is acting as a repressor. 4. Changes in the Introduction and Discussion to better place this finding in context of previous work. 5. Removed data on unc-86 and rnt-1 suppressors, which will now be the focus of a separate manuscript. 6. Formatting error in v.2 Dec 13 2020 caused loss of some in-text references. This is corrected in v.3 Dec 14 2020.