title: Analysis of sphingosine-1-phosphate signaling mutants reveals endodermal requirements for the growth but not dorsoventral patterning of jaw skeletal precursors.
abstract: 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.
authors.affiliation: Eli and Edythe Broad Institute for Regenerative Medicine and Stem Cell Research, Department of Cell and Neurobiology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Balczerski
authors.forename: Megan
authors.initials: M
authors.lastname: Matsutani
authors.forename: Pablo
authors.initials: P
authors.lastname: Castillo
authors.forename: Nick
authors.initials: N
authors.lastname: Osborne
authors.forename: Didier Y R
authors.initials: DY
authors.lastname: Stainier
authors.forename: J Gage
authors.initials: JG
authors.lastname: Crump
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D019465:Craniofacial Abnormalities / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004707:Endoderm / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005838:Genotype; D053823:Hedgehog Proteins / Q000378:metabolism; D007090:Image Interpretation, Computer-Assisted; D017403:In Situ Hybridization; D007568:Jaw / Q000196:embryology*; D008246:Lysophospholipids / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009154:Mutation / Q000235:genetics; D049349:Receptors, Lysosphingolipid / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D053823:Hedgehog Proteins; D008246:Lysophospholipids; D008565:Membrane Proteins; D049349:Receptors, Lysosphingolipid; C524053:Shha protein, zebrafish; D029961:Zebrafish Proteins; C517774:fgf8a protein, zebrafish; C534950:sphingolipid transporter 2, zebrafish; C060506:sphingosine 1-phosphate; D005346:Fibroblast Growth Factors; D013110:Sphingosine