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Zebra.ish Wnt9b Pa.terns the First Pha.yngea. a.ch into D-I-V Doma.ns a.d Promotes a.terior-Media. Outgrowth

a.erica. Journa. of Molecula. Biology 2015年第3期5卷 57-83页

作者： Henry Wells Ja.kson Diva.a. Pra.a.h Ma.k Lita.er Tra.ie Ferreira.peter a. jezewski Depa.tment of Genetics University of Alabama at Birmingham Birmingham USA University of a.a.a.a.a. Birmingha. School of Dentistry Institute of Oral Health Research Birmingham USA Depa.tment of Clinica. a.d Community Sciences University of Alabama at Birmingham School of Dentistry Birmingham USA Depa.tment of Bioengineering University of Massachusetts Dartmouth Dartmouth MA USA Depa.tment of Pedia.ric Dentistry University of Alabama at Birmingham School of Dentistry Birmingham AL USA

Disrupted morphogenesis a.d growth of the embryonic ma.illa.y ja. lea. to ora. fa.ia. clefting in huma.s (OFC) a.d result in a. incompletely formed seconda.y mouth a.d fa.e. a.requirement for Wnt signa.ing a.d Wnt9b in pa.ticula. a.e postula.ed in the etiology of OFC from a.socia.ion studies in huma.s a.d from a.ima. models. Loss of murine Wnt9b lea.s to reduced upper ja. (ma.illa.y) outgrowth a.d OFC, though the signa.ing a.chitecture lea.ing to this phenotype is poorly understood. Previous murine Wnt9b studies la.gely overlooked cra.ia. neura. crest cell (CNCC) pa.terning events a.d instea. focused on la.er events during fusion of fa.ia. prominences. Using zebra.ish a.d a.morpholino-media.ed knockdown a.proa.h, we demonstra.e functiona. requirements for Wnt9b signa.ing during two crucia. sta.es of fa.ia. development: 1) CNCC pa.terning into Dorsa.-Intermedia.e-Ventra. (D-I-V) doma.ns;a.d 2) fa.ia. outgrowth during the prima.y to seconda.y mouth tra.sition (PM to SM). Zebra.ish embryos deficient for Wnt9b (Wnt9b morpha.ts) exhibit a. open bite with fused ja. joints a. well a. a.fla. fa.e. Open bite a.d ja. joint fusion in Wnt9b morpha.ts phenocopies cha.a.teristics of edn1 pa.hwa. is muta.t zebra.ish with disrupted D-I-V pa.terning of CNCC. Expression studies show Wnt9b morpha.ts exhibit perturbed expression of edn1 signa.ing ta.gets including dlx2a. ja.1b, a.d msxe, consistent with disrupted CNCC pa.terning. Wnt9b morpha.t upper ja.s ha.e stunted outgrowth reminiscent of murine Wnt9b muta.ts a.d Wnt9b morpha.t skulls phenocopy the broa. cla.s of foreshortened skull zebra.ish muta.ts known a. ha.merhea.s. Wnt9b morpha.ts show upregula.ed expression of pitx2a.a.ter the opening of the prima.y mouth a.d disrupted expression of Wnt5b which is consistent with disrupted chondrocyte sta.king. Strong upregula.ion of dorsa. mesoderma. frzb expression in the prechorda. pla.e of Wnt9b morpha.ts suggests a.role for Wnt9b in prima.y mouth induction or ma.ntena.ce. Collectively

关键词： Cleft Morphogenesis Pa.terning Cra.ia. Neura. Crest Cell Pha.yngea. a.ch Prima.y/Seconda.y Mouth

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Ea.ly expression of the <i>tbx</i>22 gene in zebra.ish influences positioning of pha.yngea. a.ch ca.tila.es

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a.erica. Journa. of Molecula. Biology 2012年第4期2卷 318-331页

作者： Ta.my Lynne Silva.a.gela.a.la.d Cox V. P. Boomina.ha. peter a.a. jezewski Tra.ie Lee Ferreira Depa.tment of Biology University of Massachusetts Dartmouth Dartmouth USA Depa.tment of Bioengineering University of Massachusetts Dartmouth Dartmouth USA Depa.tment of Periodontology Institute of Oral Health Research University of Alabama at Birmingham Birmingham USA

Muta.ions in huma. TBX22 ca.se X-linked cleft pa.a.e with a.klyoglossia.syndrome. The two zebra.ish tbx22 splice isoforms, tbx22-1 a.d tbx22-2, encode proteins of 444 a.d 400 a.ino a.ids, respectively. Zebra.ish tbx22 mRNa.expression mirrors ma.ma.ia. TBX22 expression a.d is consistent with ea.ly pa.terning of the vertebra.e fa.e. In zebra.ish, tbx22 mRNa.is strongly expressed during ea.ly pha.yngea. a.ch development in the ventra. mesenchyme, a.d a.la.er expression doma.n is found in ectomesenchyma. cells underlying the stomodeum, a.bila.ina. epithelia. structure dema.ca.ing the ea.ly forming mouth. Therefore, tbx22 is hypothesized to be involved in cra.iofa.ia. development. The objective of this work is to cha.a.terize the role of tbx22 during cra.iofa.ia. development in zebra.ish. Tbx22 knockdown revea.ed tha. defects in tbx22 signa.ing ca.se mild clefting, joint defects a.d dorsoventra. pa.terning defects in ca.tila.es. Qua.tita.ive PCR a.d in situ a.a.ysis revea.ed tha. knockdown of tbx22 a.so ca.ses a.dra.a.ic decrea.e in expression of osr1 a.d gdf5. Cra.iofa.ia. pa.terning is dependent on proper signa.s from endoderm, mesoderm a.d ectoderm. The ea.ly influence of tbx22 on signa.s within the ventra. mesenchyme impa.ts the doma.ns of severa. key pha.ynx-gea. a.ch signa.s, thereby helping to regula.e proper pa.terning of the developing ja..

关键词： Zebra.ish Tbx Signa.ing Pha.yngea. Pouch

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