Neural Crest Specification by Prohibitin1 Depends on Transcriptional Regulation of prl3 and vangl1

作者：Deichmann Christina; Link Martina; Seyfang Melanie; Knotz Viktoria; Gradl Dietmar; Wedlich Doris

来源：GENESIS, 2015, 53(10): 627-639.

DOI：10.1002/dvg.22883

<jats:title>Summary</jats:title><jats:p>A complex network of transcription factors regulates specification of neural crest cells at early neurula stage by stabilizing neural crest identity and activating neural crest effector genes so that distinct subpopulations evolve. In this network, <jats:italic>c‐myc</jats:italic> acts on top of the gene hierarchy controlling <jats:italic>snail2, AP2</jats:italic> and <jats:italic>prohibitin1</jats:italic> (<jats:italic>phb1</jats:italic>) expression. While <jats:italic>snail2</jats:italic> and <jats:italic>AP2</jats:italic> are well studied neural crest specifier genes little is known about the role of <jats:italic>phb1</jats:italic> in this process. To identify <jats:italic>phb1</jats:italic> regulated genes we analyzed the transcriptome of neural crest explants of <jats:italic>phb1</jats:italic> morphant <jats:italic>Xenopus</jats:italic> embryos. Among 147 <jats:italic>phb1</jats:italic> regulated genes we identified the membrane‐associated protein‐tyrosine phosphatase <jats:italic>PRP4A3</jats:italic> (<jats:italic>prl3</jats:italic>) and the atypical cadherin and Wnt‐PCP component <jats:italic>van gogh like1</jats:italic> (<jats:italic>vangl1</jats:italic>). Gain of function, loss of function and epistasis experiments allowed us to allocate both genes in the neural crest specification network between <jats:italic>phb1</jats:italic> and <jats:italic>twist</jats:italic>. Interestingly, both, <jats:italic>vangl1</jats:italic> and <jats:italic>prl3</jats:italic> regulate only a small subset of neural crest marker genes. The identification of two membrane‐associated proteins as novel neural crest specifiers indicates that in addition to gene regulation by combinatory effects of transcription factors also post‐translational modifications (<jats:italic>prl3</jats:italic>) and cell–cell adhesion and/or regulation of cell‐polarity (<jats:italic>vangl1</jats:italic>) specify the identity of neural crest cell populations. genesis 53:627–639, 2015.

• 出版日期2015-10