Elk3 is essential for the progression from progenitor to definitive neural crest cell

Elk3/Net/Sap2 (here referred to as Elk3) is an Ets ternary complex transcriptional repressor known for its involvement in angiogenesis during embryonic development. Although Elk3 is expressed in various tissues, additional roles for the protein outside of vasculature development have yet to be reported. Here, we characterize the early spatiotemporal expression pattern of Elk3 in the avian embryo using whole mount in situ hybridization and quantitative RT-PCR and examine the effects of its loss of function on neural crest development. At early stages, Elk3 is expressed in the head folds, head mesenchyme, intersomitic vessels, and migratory cranial neural crest (NC) cells. Loss of the Elk3 protein results in the retention of Pax7+ precursors in the dorsal neural tube that fail to upregulate neural crest specifier genes, FoxD3, Sox10 and Snail2, resulting in embryos with severe migration defects. The results putatively place Elk3 downstream of neural plate border genes, but upstream of neural crest specifier genes in the neural crest gene regulatory network (NC-GRN), suggesting that it is critical for the progression from progenitor to definitive neural crest cell.

► Elk3 is expressed in the neural folds prior to neural crest EMT, and in the migratory crest during early avian development.
► Elk3 is required for neural crest specification marked by FoxD3 and Sox10.
► Loss of Elk3 leads to the maintenance of Pax7 positive, but FoxD3/Sox10 negative cells in the dorsal neural tube.
► Elk3 is required in the NC-GRN downstream of NC border genes and upstream of NC specifiers.