ABSTRACT
During convergent differentiation, multiple developmental lineages produce a highly similar or identical cell type. However, few molecular players that drive convergent differentiation are 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 or function. 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 early and specifically in one convergent lineage to produce a cell type that also arises from molecularly distinct progenitors in other lineages.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
1. Additional analysis regarding the identity and possible origins of the ectopic AMso glial cell in unc-130 mutants has been added to Fig. S2. Briefly: (i) it expresses the pan-glial marker mir-228; (ii) although the transcription factor gene lin-48 is expressed both by the endogenous and ectopic AMso, it is not required for their specification; (iii) it is located near the position where the ILsoD glia would normally be; (iv) unc-130 mutants do not form an ectopic CEM (the AMso sister cell), suggesting that a lineage duplication is not the source of the extra AMso. 2. The expression of UNC-130 across the full embryonic lineage has been added as Fig. S3, and quantification of the effects of unc-130 on expression of IL1 and IL2 specific markers has been added to Table S2. 3. Additional data on role of UNC-37 in UNC-130-mediated repression has been added to Fig. S5. Briefly: (i) UNC-37/Groucho is required for the rescuing activity of the N-terminal portion of UNC-130, which contains an eh1 motif; and (ii) either the eh1 motif nor UNC-37 are required for activity of full-length UNC-130, consistent with the presence of a redundant (and UNC-37-independent) repressive activity in its C-terminal portion. 4. Additional clarifications and revisions have been made throughout the text.