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Using the antiphosphatase Paladin to understand the phosphoregulation of neural crest development
Author(s) -
RoffersAgarwal Julaine,
Hutt Karla J.,
Gammill Laura S.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.965.3
Subject(s) - neural crest , neural tube , neural fold , biology , neural plate , population , crest , neuroscience , microbiology and biotechnology , embryo , medicine , physics , environmental health , quantum mechanics
The neural crest is a migratory embryonic cell population that arises in the dorsal neural tube and gives rise to diverse cell types including peripheral nerves, glia and melanocytes. While the network of transcription factors (TFs) responsible for neural crest development has been established, expression of these TFs does not guarantee that a dorsal neural tube cell will become a migratory neural crest cell. We propose that subsequent modulation of protein activity through phosphorylation also regulates the establishment of neural crest cell fate. Paladin, a novel protein containing two consensus phosphatase active site motifs, is expressed throughout neural crest development and influences the expression of a subset of neural crest TFs. Both gain and loss of Paladin function disrupt early neural crest migration. Mutational analysis reveals that critical catalytic cysteine residues are dispensable for Paladin function, revealing Paladin as an antiphosphatase. Together these data identify Paladin as a unique regulator of neural crest specification and migration. We are currently utilizing Paladin to identify new neural crest regulatory factors that are modulated by phosphorylation using both in vitro and in vivo assays, thus expanding our understanding of an underappreciated level of control within the neural crest developmental program. Funding: NIH F32DE019973; K22DE015309. Grant Funding Source : NIH