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© Research
Publication : eLife

Dullard-mediated Smad1/5/8 inhibition controls mouse cardiac neural crest cells condensation and outflow tract septation

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in eLife - 27 Feb 2020

Darrigrand JF, Valente M, Comai G, Martinez P, Petit M, Nishinakamura R, Osorio DS, Gilles R, Marchiol C, Ribes V, Cadot B

Link to Pubmed [PMID] – 32105214

Elife 2020 Feb;9

The establishment of separated pulmonary and systemic circulation in vertebrates, via the cardiac outflow tract (OFT) septation is a sensitive developmental process accounting for 10% of all congenital anomalies. Neural Crest Cells (NCC) colonising the heart condensate along the primitive endocardial tube and force its scission into two tubes. Here, we show that NCC aggregation progressively decreases along the OFT distal-proximal axis following a BMP signalling gradient. Dullard, a nuclear phosphatase, tunes the BMP gradient amplitude and prevents NCC premature condensation. Dullard maintains transcriptional programs providing NCC with mesenchymal traits. It attenuates the expression of the aggregation factor and conversely promotes that of the epithelial-mesenchymal transition driver . Altogether, Dullard-mediated fine-tuning of BMP signalling ensures the timed and progressive zipper-like closure of the OFT by the NCC and prevents the formation of an heart carrying the four congenital abnormalities defining the tetralogy of Fallot.

https://www.ncbi.nlm.nih.gov/pubmed/32105214