title: Zebrafish foxd3 is selectively required for neural crest specification, migration and survival.
abstract: The vertebrate neural crest is a pluripotent cell population that generates a large variety of cell types, including peripheral neurons, cartilage and pigment cells. Mechanisms that control the patterning of the neural crest toward specific cell fates remain only partially understood. Zebrafish homozygous for the sympathetic mutation 1 (sym1) have defects in a subset of neural crest derivatives, such as peripheral neurons, glia and cartilage, but retain normal numbers of melanocytes. The sym1 mutation is a nucleotide deletion that disrupts the forkhead DNA-binding domain of the foxd3 gene, which encodes a conserved winged-helix transcription factor. We show that sym1 mutants have normal numbers of premigratory neural crest cells, but these cells express reduced levels of snai1b and sox10, implicating foxd3 as an essential regulator of these transcription factors in the premigratory neural crest. The onset of neural crest migration is also delayed in sym1 mutants, and there is a reduction in the number of migratory trunk neural crest cells, particularly along the medial migration pathway. TUNEL analysis revealed aberrant apoptosis localized to the hindbrain neural crest at the 15-somite stage, indicating a critical role for foxd3 in the survival of a subpopulation of neural crest cells. These results show that foxd3 selectively specifies premigratory neural crest cells for a neuronal, glial or cartilage fate, by inducing the expression of lineage-associated transcription factors in these cells and regulating their subsequent migration.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Stewart
authors.forename: Brigitte L
authors.initials: BL
authors.lastname: Arduini
authors.forename: Stephane
authors.initials: S
authors.lastname: Berghmans
authors.forename: Rani E
authors.initials: RE
authors.lastname: George
authors.forename: John P
authors.initials: JP
authors.lastname: Kanki
authors.forename: Paul D
authors.initials: PD
authors.lastname: Henion
authors.forename: A Thomas
authors.initials: AT
authors.lastname: Look
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D005260:Female; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009432:Neural Crest / Q000166:cytology* / Q000196:embryology* / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis / Q000502:physiology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000502:physiology; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D051858:Forkhead Transcription Factors; D014157:Transcription Factors; D029961:Zebrafish Proteins; C491002:foxd3 protein, zebrafish