Requirement for frzb and fzd7a in cranial neural crest convergence and extension mechanisms during zebrafish palate and jaw morphogenesis

Kamel, G., Hoyos, T., Rochard, L., Dougherty, M., Tse, W., Shubinets, V., Grimaldi, M., and Liao, E.C.
Developmental Biology   381(2): 423-33 (Journal)
Registered Authors
Liao, Eric, Tse, Ka Fai William
convergence extension, wnt, frizzled, frzb, fzd7a, Wnt9a, cranial neural crest, craniofacial, zebrafish
MeSH Terms
  • Animals
  • Apoptosis
  • Body Patterning
  • Cell Proliferation
  • Chondrocytes/metabolism
  • Embryo, Nonmammalian/metabolism
  • Epistasis, Genetic
  • Gene Expression Regulation, Developmental
  • Glycoproteins/genetics
  • Glycoproteins/metabolism*
  • HEK293 Cells
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism
  • Humans
  • Jaw/embryology*
  • Jaw/metabolism
  • Morphogenesis
  • Neural Crest/embryology
  • Neural Crest/metabolism*
  • Palate/growth & development*
  • Palate/metabolism
  • Receptors, Cell Surface/genetics
  • Receptors, Cell Surface/metabolism*
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
23806211 Full text @ Dev. Biol.

Regulation of convergence and extension by wnt-frizzled signaling is a common theme in embryogenesis. This study examines the functional requirements of frzb and fzd7a in convergence and extension mechanisms during craniofacial development. Using a morpholino knockdown approach, we found that frzb and fzd7a are dispensable for directed migration of the bilateral trabeculae, but necessary for the convergence and extension of the palatal elements, where the extension process is mediated by chondrocyte proliferation, morphologic change and intercalation. In contrast, frzb and fzd7a are required for convergence of the mandibular prominences, where knockdown of either frzb or fzd7a resulted in complete loss of lower jaw structures. Further, we found that bapx1 was specifically downregulated in the wnt9a/frzb/fzd7a morphants, while general neural crest markers were unaffected. In addition, expression of wnt9a and frzb was also absent in the edn/ mutant. Notably, over-expression of bapx1 was sufficient to partially rescue mandibular elements in the wnt9a/frzb/fzd7a morphants, demonstrating genetic epistasis of bapx1 acting downstream of edn1 and wnt9a/frzb/fzd7a in lower jaw development. This study underscores the important role of wnt-frizzled signaling in convergence and extension in palate and craniofacial morphogenesis, distinct regulation of upper vs. lower jaw structures, and integration of wnt-frizzled with endothelin signaling to coordinate shaping of the facial form.

Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes