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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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Zygotic FoxK activity is necessary for midgut differentiation. Midgut development in wild-type (A, D, and G), FoxK44 (B, E, and H), and FoxK16 (C, F, and I) embryos. In FoxK44 and FoxK16 homozygous embryos, the single vesicle of the midgut develops normally until stage 15 (A–C, dashed lines). During stages 16 and 17, wild-type embryos develop four vesicles after the formation of the midgut constrictions (D and G, arrowheads). However, FoxK44 homozygous embryos only develop one midgut constriction (E and H, arrowheads), whereas FoxK16 embryos never develop midgut constrictions (F and I). (J–O) Maternal FoxK is critical for early embryonic development. Differential interference contrast (J–L) and confocal images showing Engrailed (En) expression (M–O) of a normal embryo (J and M) and two different embryos expressing FoxKi under a maternally expressed Gal4-VP16 fusion (tub-Gal4-VP16/UAS-Foxki). The segmental Engrailed stripes are fused (N, arrowhead), split (N and O, arrows), and generally disorganized along the anteroposterior axis.
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fig5: Zygotic FoxK activity is necessary for midgut differentiation. Midgut development in wild-type (A, D, and G), FoxK44 (B, E, and H), and FoxK16 (C, F, and I) embryos. In FoxK44 and FoxK16 homozygous embryos, the single vesicle of the midgut develops normally until stage 15 (A–C, dashed lines). During stages 16 and 17, wild-type embryos develop four vesicles after the formation of the midgut constrictions (D and G, arrowheads). However, FoxK44 homozygous embryos only develop one midgut constriction (E and H, arrowheads), whereas FoxK16 embryos never develop midgut constrictions (F and I). (J–O) Maternal FoxK is critical for early embryonic development. Differential interference contrast (J–L) and confocal images showing Engrailed (En) expression (M–O) of a normal embryo (J and M) and two different embryos expressing FoxKi under a maternally expressed Gal4-VP16 fusion (tub-Gal4-VP16/UAS-Foxki). The segmental Engrailed stripes are fused (N, arrowhead), split (N and O, arrows), and generally disorganized along the anteroposterior axis.

Mentions: To determine the reason for the lethality of the FoxK alleles, we analyzed the development of FoxK16 homozygous embryos at different stages. Although FoxK presented a widespread distribution in developing embryos, we found no obvious morphological abnormalities in early and intermediate stages of development. However, midgut differentiation was abnormal in late FoxK mutant embryos. Early midgut development was normal in both FoxK16 and FoxK44 mutant embryos until stage 15, when the midgut was comprised of a single vesicle (Fig. 5, A–C, dashed line). During stage 16 three constrictions generated the four vesicles of the normal midgut (Fig. 5 D). However, FoxK44 homozygous embryos formed a single midgut constriction and two gastric vesicles (Fig. 5 E), whereas FoxK16 embryos failed to complete the first midgut constriction (Fig. 5 F). Later on, wild-type embryos formed the mature midgut compartments in stage 17 (Fig. 5 G), but the midgut did not further develop in either FoxK44 or FoxK16 homozygous embryos (Fig. 5, H and I). Thus, FoxK activity is required for the formation of the midgut constrictions and for the proper development of the midgut vesicles.


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)

Zygotic FoxK activity is necessary for midgut differentiation. Midgut development in wild-type (A, D, and G), FoxK44 (B, E, and H), and FoxK16 (C, F, and I) embryos. In FoxK44 and FoxK16 homozygous embryos, the single vesicle of the midgut develops normally until stage 15 (A–C, dashed lines). During stages 16 and 17, wild-type embryos develop four vesicles after the formation of the midgut constrictions (D and G, arrowheads). However, FoxK44 homozygous embryos only develop one midgut constriction (E and H, arrowheads), whereas FoxK16 embryos never develop midgut constrictions (F and I). (J–O) Maternal FoxK is critical for early embryonic development. Differential interference contrast (J–L) and confocal images showing Engrailed (En) expression (M–O) of a normal embryo (J and M) and two different embryos expressing FoxKi under a maternally expressed Gal4-VP16 fusion (tub-Gal4-VP16/UAS-Foxki). The segmental Engrailed stripes are fused (N, arrowhead), split (N and O, arrows), and generally disorganized along the anteroposterior axis.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2600746&req=5

fig5: Zygotic FoxK activity is necessary for midgut differentiation. Midgut development in wild-type (A, D, and G), FoxK44 (B, E, and H), and FoxK16 (C, F, and I) embryos. In FoxK44 and FoxK16 homozygous embryos, the single vesicle of the midgut develops normally until stage 15 (A–C, dashed lines). During stages 16 and 17, wild-type embryos develop four vesicles after the formation of the midgut constrictions (D and G, arrowheads). However, FoxK44 homozygous embryos only develop one midgut constriction (E and H, arrowheads), whereas FoxK16 embryos never develop midgut constrictions (F and I). (J–O) Maternal FoxK is critical for early embryonic development. Differential interference contrast (J–L) and confocal images showing Engrailed (En) expression (M–O) of a normal embryo (J and M) and two different embryos expressing FoxKi under a maternally expressed Gal4-VP16 fusion (tub-Gal4-VP16/UAS-Foxki). The segmental Engrailed stripes are fused (N, arrowhead), split (N and O, arrows), and generally disorganized along the anteroposterior axis.
Mentions: To determine the reason for the lethality of the FoxK alleles, we analyzed the development of FoxK16 homozygous embryos at different stages. Although FoxK presented a widespread distribution in developing embryos, we found no obvious morphological abnormalities in early and intermediate stages of development. However, midgut differentiation was abnormal in late FoxK mutant embryos. Early midgut development was normal in both FoxK16 and FoxK44 mutant embryos until stage 15, when the midgut was comprised of a single vesicle (Fig. 5, A–C, dashed line). During stage 16 three constrictions generated the four vesicles of the normal midgut (Fig. 5 D). However, FoxK44 homozygous embryos formed a single midgut constriction and two gastric vesicles (Fig. 5 E), whereas FoxK16 embryos failed to complete the first midgut constriction (Fig. 5 F). Later on, wild-type embryos formed the mature midgut compartments in stage 17 (Fig. 5 G), but the midgut did not further develop in either FoxK44 or FoxK16 homozygous embryos (Fig. 5, H and I). Thus, FoxK activity is required for the formation of the midgut constrictions and for the proper development of the midgut vesicles.

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