title: An early requirement for maternal FoxH1 during zebrafish gastrulation.
abstract: The Forkhead Box H1 (FoxH1) protein is a co-transcription factor recruited by phosphorylated Smad2 downstream of several TGFbetas, including Nodal-related proteins. We have reassessed the function of zebrafish FoxH1 using antisense morpholino oligonucleotides (MOs). MOs targeting translation of foxH1 disrupt embryonic epiboly movements during gastrulation and cause death on the first day of development. The FoxH1 morphant phenotype is much more severe than that of zebrafish carrying foxh1/schmalspur (sur) DNA-binding domain mutations, FoxH1 splice-blocking morphants or other Nodal pathway mutants, and it cannot be altered by concomitant perturbations in Nodal signaling. Apart from disrupting epiboly, FoxH1 MO treatment disrupts convergence and internalization movements. Late gastrula-stage FoxH1 morphants exhibit delayed mesoderm and endoderm marker gene expression and failed patterning of the central nervous system. Probing FoxH1 morphant RNA by microarray, we identified a cohort of five keratin genes--cyt1, cyt2, krt4, krt8 and krt18--that are normally transcribed in the embryo's enveloping layer (EVL) and which have significantly reduced expression in FoxH1-depleted embryos. Simultaneously disrupting these keratins with a mixture of MOs reproduces the FoxH1 morphant phenotype. Our studies thus point to an essential role for maternal FoxH1 and downstream keratins during gastrulation that is epistatic to Nodal signaling.
authors: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 9000 Rockville Pike, Building 35, Room 1B 205, Bethesda, MD 20892, USA.
authors: Wuhong
authors: W
authors: Pei
authors: Houtan
authors: H
authors: Noushmehr
authors: Justin
authors: J
authors: Costa
authors: Maia V
authors: MV
authors: Ouspenskaia
authors: Abdel G
authors: AG
authors: Elkahloun
authors: Benjamin
authors: B
authors: Feldman
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000502:physiology; D004627:Embryonic Induction; D051858:Forkhead Transcription Factors / Q000502:physiology*; D054262:Gastrulation / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D007633:Keratins / Q000235:genetics*; D055457:Nodal Protein; D016376:Oligonucleotides, Antisense; D015398:Signal Transduction; D051899:Smad2 Protein / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D015027:Zebrafish / Q000196:embryology* / Q000502:physiology; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: D051858:Forkhead Transcription Factors; D055457:Nodal Protein; D016376:Oligonucleotides, Antisense; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; C491116:foxh1 protein, zebrafish; C497786:smad2 protein, zebrafish; D007633:Keratins
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