Xenopus Id3 is required downstream of Myc for the formation of multipotent neural crest progenitor cells.
Neural crest cells, a population of proliferative, migratory, tissue-invasive stem cells, are a defining feature of vertebrate embryos. These cells arise at the neural plate border during a time in development when precursors of the central nervous system and the epidermis are responding to the extracellular signals that will ultimately dictate their fates. Neural crest progenitors, by contrast, must be maintained in a multipotent state until after neural tube closure. Although the molecular mechanisms governing this process have yet to be fully elucidated, recent work has suggested that Myc functions to prevent premature cell fate decisions in neural crest forming regions of the early ectoderm. Here, we show that the small HLH protein Id3 is a Myc target that plays an essential role in the formation and maintenance of neural crest stem cells. A morpholino-mediated 'knockdown' of Id3 protein results in embryos that lack neural crest. Moreover, forced expression of Id3 maintains the expression of markers of the neural crest progenitor state beyond the time when they would normally be downregulated and blocks the differentiation of neural crest derivatives. These results shed new light on the mechanisms governing the formation and maintenance of a developmentally and clinically important cell population.
Light
William
W
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208, USA.
Vernon
Ann E
AE
Lasorella
Anna
A
Iavarone
Antonio
A
LaBonne
Carole
C
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D016259:Genes, myc / Q000235:genetics; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D047468:Immunoprecipitation; D020287:In Situ Nick-End Labeling; D051796:Inhibitor of Differentiation Proteins; D009432:Neural Crest / Q000166:cytology / Q000196:embryology*; D009841:Oligonucleotides; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology* / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
C501325:Id3 protein, Xenopus; D051796:Inhibitor of Differentiation Proteins; D009841:Oligonucleotides; D014157:Transcription Factors; D029867:Xenopus Proteins