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FoxK mediates TGF-beta signalling during midgut differentiation in flies.

Casas-Tinto S, Gomez-Velazquez M, Granadino B, Fernandez-Funez P - J. Cell Biol. (2008)

Bottom Line: Genet.This regulatory activity does not require direct labial activation by the TGF-beta effector Mad.Thus, we propose that the combined activity of the TGF-beta target genes FoxK and Dfos is critical for the direct activation of lab in the endoderm.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555, USA. scasas@cnio.es

ABSTRACT
Inductive signals across germ layers are important for the development of the endoderm in vertebrates and invertebrates (Tam, P.P., M. Kanai-Azuma, and Y. Kanai. 2003. Curr. Opin. Genet. Dev. 13:393-400; Nakagoshi, H. 2005. Dev. Growth Differ. 47:383-392). In flies, the visceral mesoderm secretes signaling molecules that diffuse into the underlying midgut endoderm, where conserved signaling cascades activate the Hox gene labial, which is important for the differentiation of copper cells (Bienz, M. 1997. Curr. Opin. Genet. Dev. 7:683-688). We present here a Drosophila melanogaster gene of the Fox family of transcription factors, FoxK, that mediates transforming growth factor beta (TGF-beta) signaling in the embryonic midgut endoderm. FoxK mutant embryos fail to generate midgut constrictions and lack Labial in the endoderm. Our observations suggest that TGF-beta signaling directly regulates FoxK through functional Smad/Mad-binding sites, whereas FoxK, in turn, regulates labial expression. We also describe a new cooperative activity of the transcription factors FoxK and Dfos/AP-1 that regulates labial expression in the midgut endoderm. This regulatory activity does not require direct labial activation by the TGF-beta effector Mad. Thus, we propose that the combined activity of the TGF-beta target genes FoxK and Dfos is critical for the direct activation of lab in the endoderm.

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Peptidic sequence and genomic structure of Drosophila FoxK. (A) Sequence alignment of the FH domains of Drosophila FoxK, human ILF, and murine MNF. Identical and conserved amino acids are indicated in black shading. The bipartite nuclear localization sequence (NLS) is indicated in red. The three α helices (H1–3) and the two winged loops (W1 and 2) are also indicated. (B) Amino acid conservation between full-length FoxK and human ILF. Conservation in the FHA and FH domains is indicated. (C) Full-length amino acid sequence of FoxK-L. The FHA and FH domains (both in red) are indicated (FH underlined). Sequence encoded by the alternatively spliced exons 8 and 9 absent in FoxK-S is shown in green. (D) Exon/intron structure of FoxK with the four alternative 5′UTRs (black boxes). The coding region of FoxK extends from exon 2 (ATG) to exon 9 (TGA). The FHA and FH domains are indicated. (E) Structure of FoxK-L transcripts. The hypothetical FoxK-L-RE mRNA lacks part of exon 6. (F) Structure of the FoxK-S transcripts. An alternative splicing that lacks 258 nucleotides between exons 8 and 9 (C and D, green) generates four different FoxK-S mRNAs.
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fig1: Peptidic sequence and genomic structure of Drosophila FoxK. (A) Sequence alignment of the FH domains of Drosophila FoxK, human ILF, and murine MNF. Identical and conserved amino acids are indicated in black shading. The bipartite nuclear localization sequence (NLS) is indicated in red. The three α helices (H1–3) and the two winged loops (W1 and 2) are also indicated. (B) Amino acid conservation between full-length FoxK and human ILF. Conservation in the FHA and FH domains is indicated. (C) Full-length amino acid sequence of FoxK-L. The FHA and FH domains (both in red) are indicated (FH underlined). Sequence encoded by the alternatively spliced exons 8 and 9 absent in FoxK-S is shown in green. (D) Exon/intron structure of FoxK with the four alternative 5′UTRs (black boxes). The coding region of FoxK extends from exon 2 (ATG) to exon 9 (TGA). The FHA and FH domains are indicated. (E) Structure of FoxK-L transcripts. The hypothetical FoxK-L-RE mRNA lacks part of exon 6. (F) Structure of the FoxK-S transcripts. An alternative splicing that lacks 258 nucleotides between exons 8 and 9 (C and D, green) generates four different FoxK-S mRNAs.

Mentions: Our study of the Drosophila orthologue of FOXK1 determined that its FH domain shares 84% sequence conservation to both human and murine FOXK1 and contains a characteristic bipartite nuclear localization sequence (Fig. 1, A and B). The N-terminal portion of Drosophila FoxK also contains a conserved FH-associated domain (FHA; Fig. 1, B and C), a phosphoprotein-binding domain typically found in the FOXK subfamily and in other proteins (Durocher and Jackson, 2002). Drosophila FoxK shares 67% identity in the FHA domain with human ILF/FOXK1, whereas the overall conservation of the full-length sequence is 48% (Fig. 1 B).


FoxK mediates TGF-beta signalling during midgut differentiation in flies.

Casas-Tinto S, Gomez-Velazquez M, Granadino B, Fernandez-Funez P - J. Cell Biol. (2008)

Peptidic sequence and genomic structure of Drosophila FoxK. (A) Sequence alignment of the FH domains of Drosophila FoxK, human ILF, and murine MNF. Identical and conserved amino acids are indicated in black shading. The bipartite nuclear localization sequence (NLS) is indicated in red. The three α helices (H1–3) and the two winged loops (W1 and 2) are also indicated. (B) Amino acid conservation between full-length FoxK and human ILF. Conservation in the FHA and FH domains is indicated. (C) Full-length amino acid sequence of FoxK-L. The FHA and FH domains (both in red) are indicated (FH underlined). Sequence encoded by the alternatively spliced exons 8 and 9 absent in FoxK-S is shown in green. (D) Exon/intron structure of FoxK with the four alternative 5′UTRs (black boxes). The coding region of FoxK extends from exon 2 (ATG) to exon 9 (TGA). The FHA and FH domains are indicated. (E) Structure of FoxK-L transcripts. The hypothetical FoxK-L-RE mRNA lacks part of exon 6. (F) Structure of the FoxK-S transcripts. An alternative splicing that lacks 258 nucleotides between exons 8 and 9 (C and D, green) generates four different FoxK-S mRNAs.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2600746&req=5

fig1: Peptidic sequence and genomic structure of Drosophila FoxK. (A) Sequence alignment of the FH domains of Drosophila FoxK, human ILF, and murine MNF. Identical and conserved amino acids are indicated in black shading. The bipartite nuclear localization sequence (NLS) is indicated in red. The three α helices (H1–3) and the two winged loops (W1 and 2) are also indicated. (B) Amino acid conservation between full-length FoxK and human ILF. Conservation in the FHA and FH domains is indicated. (C) Full-length amino acid sequence of FoxK-L. The FHA and FH domains (both in red) are indicated (FH underlined). Sequence encoded by the alternatively spliced exons 8 and 9 absent in FoxK-S is shown in green. (D) Exon/intron structure of FoxK with the four alternative 5′UTRs (black boxes). The coding region of FoxK extends from exon 2 (ATG) to exon 9 (TGA). The FHA and FH domains are indicated. (E) Structure of FoxK-L transcripts. The hypothetical FoxK-L-RE mRNA lacks part of exon 6. (F) Structure of the FoxK-S transcripts. An alternative splicing that lacks 258 nucleotides between exons 8 and 9 (C and D, green) generates four different FoxK-S mRNAs.
Mentions: Our study of the Drosophila orthologue of FOXK1 determined that its FH domain shares 84% sequence conservation to both human and murine FOXK1 and contains a characteristic bipartite nuclear localization sequence (Fig. 1, A and B). The N-terminal portion of Drosophila FoxK also contains a conserved FH-associated domain (FHA; Fig. 1, B and C), a phosphoprotein-binding domain typically found in the FOXK subfamily and in other proteins (Durocher and Jackson, 2002). Drosophila FoxK shares 67% identity in the FHA domain with human ILF/FOXK1, whereas the overall conservation of the full-length sequence is 48% (Fig. 1 B).

Bottom Line: Genet.This regulatory activity does not require direct labial activation by the TGF-beta effector Mad.Thus, we propose that the combined activity of the TGF-beta target genes FoxK and Dfos is critical for the direct activation of lab in the endoderm.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555, USA. scasas@cnio.es

ABSTRACT
Inductive signals across germ layers are important for the development of the endoderm in vertebrates and invertebrates (Tam, P.P., M. Kanai-Azuma, and Y. Kanai. 2003. Curr. Opin. Genet. Dev. 13:393-400; Nakagoshi, H. 2005. Dev. Growth Differ. 47:383-392). In flies, the visceral mesoderm secretes signaling molecules that diffuse into the underlying midgut endoderm, where conserved signaling cascades activate the Hox gene labial, which is important for the differentiation of copper cells (Bienz, M. 1997. Curr. Opin. Genet. Dev. 7:683-688). We present here a Drosophila melanogaster gene of the Fox family of transcription factors, FoxK, that mediates transforming growth factor beta (TGF-beta) signaling in the embryonic midgut endoderm. FoxK mutant embryos fail to generate midgut constrictions and lack Labial in the endoderm. Our observations suggest that TGF-beta signaling directly regulates FoxK through functional Smad/Mad-binding sites, whereas FoxK, in turn, regulates labial expression. We also describe a new cooperative activity of the transcription factors FoxK and Dfos/AP-1 that regulates labial expression in the midgut endoderm. This regulatory activity does not require direct labial activation by the TGF-beta effector Mad. Thus, we propose that the combined activity of the TGF-beta target genes FoxK and Dfos is critical for the direct activation of lab in the endoderm.

Show MeSH
Related in: MedlinePlus