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Analysis of sphingosine-1-phosphate signaling mutants reveals endodermal requirements for the growth but not dorsoventral patterning of jaw skeletal precursors.

Development of the head skeleton involves reciprocal interactions between cranial neural crest cells (CNCCs) and the surrounding pharyngeal endoderm and ectoderm. Whereas elegant experiments in avians have shown a prominent role for the endoderm in facial skeleton development, the relative functions of the endoderm in growth versus regional identity of skeletal precursors have remained unclear. Here we describe novel craniofacial defects in zebrafish harboring mutations in the Sphingosine-1-phospate (S1P) type 2 receptor (s1pr2) or the S1P transporter Spinster 2 (spns2), and we show that S1P signaling functions in the endoderm for the proper growth and positioning of the jaw skeleton. Surprisingly, analysis of s1pr2 and spns2 mutants, as well as sox32 mutants that completely lack endoderm, reveals that the dorsal-ventral (DV) patterning of jaw skeletal precursors is largely unaffected even in the absence of endoderm. Instead, we observe reductions in the ectodermal expression of Fibroblast growth factor 8a (Fgf8a), and transgenic misexpression of Shha restores fgf8a expression and partially rescues the growth and differentiation of jaw skeletal precursors. Hence, we propose that the S1P-dependent anterior foregut endoderm functions primarily through Shh to regulate the growth but not DV patterning of zebrafish jaw precursors.

Pubmed ID: 22185793


  • Balczerski B
  • Matsutani M
  • Castillo P
  • Osborne N
  • Stainier DY
  • Crump JG


Developmental biology

Publication Data

February 15, 2012

Associated Grants

  • Agency: NIDCR NIH HHS, Id: DE018405
  • Agency: NIDCR NIH HHS, Id: DE018405-03S1
  • Agency: NIDCR NIH HHS, Id: DE13834
  • Agency: NICHD NIH HHS, Id: HD22486
  • Agency: NHLBI NIH HHS, Id: HL54737
  • Agency: NICHD NIH HHS, Id: P01 HD022486
  • Agency: NIDCR NIH HHS, Id: R01 DE018405
  • Agency: NIDCR NIH HHS, Id: R01 DE018405-01
  • Agency: NIDCR NIH HHS, Id: R01 DE018405-02
  • Agency: NIDCR NIH HHS, Id: R01 DE018405-03
  • Agency: NIDCR NIH HHS, Id: R01 DE018405-03S1
  • Agency: NIDCR NIH HHS, Id: R01 DE018405-04
  • Agency: NIDCR NIH HHS, Id: R01 DE018405-05

Mesh Terms

  • Analysis of Variance
  • Animals
  • Body Patterning
  • Carrier Proteins
  • Craniofacial Abnormalities
  • DNA Primers
  • DNA, Complementary
  • Endoderm
  • Fibroblast Growth Factors
  • Genotype
  • Hedgehog Proteins
  • Image Interpretation, Computer-Assisted
  • In Situ Hybridization
  • Jaw
  • Lysophospholipids
  • Membrane Proteins
  • Microscopy, Fluorescence
  • Mutation
  • Receptors, Lysosphingolipid
  • Signal Transduction
  • Sphingosine
  • Zebrafish
  • Zebrafish Proteins