SNW1 as a novel regulator of BMP signalling during early embryonic development
Session type: Poster / e-Poster / Silent Theatre session
Human metastatic melanoma is a cancer of transformed melanocytes, which derive from the embryonic neural crest. In vertebrate embryos neural crest is specified at the border between neural and non-neural ectoderm in response to signals from the surrounding tissues. Our lab identified SNW1 as a factor crucial for neural crest specification during development. Overexpression, as well as depletion, of SNW1 in Xenopus and zebrafish embryos leads to a loss of the neural crest cell population. Further experiments identified SNW1 as a regulator of BMP activity at the neural plate border, but not as a core component of the pathway downstream of the receptor. Depletion of SNW1 in zebrafish does not affect bmp2b ligand transcription, but prevents expression of the protein. Thus, SNW1 is required for a step between transcription and expression of the BMP ligands.
To address the role of SNW1 in regulation of BMP signalling we use developmental models such as Xenopus and zebrafish in combination with molecular biology (Western blot, qRT-PCR, RNAseq), Mass Spectrometry analysis and cell culture models (including melanoma).
In zebrafish and tissue culture cells depletion of SNW1 results in decreased levels of BMP2b/BMP2 protein expression. Moreover, overexpression of SNW1 increases BMP2 expression in tissue culture cells. Mass Spectrometry analysis has shown that SNW1 is in a complex with components of the splicing machinery, especially as a part of the CDC5/Prp19 subcomplex, which is found in the activated spliceosome as well as the post-spliceosomal intron complex. Additionally, SNW1 interacts with several chromatin remodeling components and transcriptional elongation factors, which might suggest a broader role of SNW1 in transcriptional processes.
Therefore, we propose that SNW1 is a critical regulator of localised BMP activity during development by functioning in the post-transcriptional regulation of bmp2b ligands. The relevance of SNW1 expression and BMP signalling in melanoma will be discussed.