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Pbx1/Pbx2requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution andShhexpression
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| Zeitschriftentitel: | Development |
|---|---|
| Personen und Körperschaften: | , , , , , , , |
| In: | Development, 133, 2006, 11, S. 2263-2273 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
The Company of Biologists
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| Schlagwörter: |
| author_facet |
Capellini, Terence D. Di Giacomo, Giuseppina Salsi, Valentina Brendolan, Andrea Ferretti, Elisabetta Srivastava, Deepak Zappavigna, Vincenzo Selleri, Licia Capellini, Terence D. Di Giacomo, Giuseppina Salsi, Valentina Brendolan, Andrea Ferretti, Elisabetta Srivastava, Deepak Zappavigna, Vincenzo Selleri, Licia |
|---|---|
| author |
Capellini, Terence D. Di Giacomo, Giuseppina Salsi, Valentina Brendolan, Andrea Ferretti, Elisabetta Srivastava, Deepak Zappavigna, Vincenzo Selleri, Licia |
| spellingShingle |
Capellini, Terence D. Di Giacomo, Giuseppina Salsi, Valentina Brendolan, Andrea Ferretti, Elisabetta Srivastava, Deepak Zappavigna, Vincenzo Selleri, Licia Development Pbx1/Pbx2requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution andShhexpression Developmental Biology Molecular Biology |
| author_sort |
capellini, terence d. |
| spelling |
Capellini, Terence D. Di Giacomo, Giuseppina Salsi, Valentina Brendolan, Andrea Ferretti, Elisabetta Srivastava, Deepak Zappavigna, Vincenzo Selleri, Licia 1477-9129 0950-1991 The Company of Biologists Developmental Biology Molecular Biology http://dx.doi.org/10.1242/dev.02395 <jats:p>Vertebrate limb development occurs along three cardinal axes–proximodistal, anteroposterior and dorsoventral–that are established via the organization of signaling centers, such as the zone of polarizing activity (ZPA). Distal limb development, in turn, requires a molecular feedback loop between the ZPA expression of sonic hedgehog(Shh) and the apical ectodermal ridge. The TALE homeoprotein Pbx1 has been shown to be essential for proximal limb development. In this study, we first uncover that Pbx1 and Pbx2 are co-expressed in the lateral plate and early limb field mesoderm. Later, Pbx2 is expressed throughout the limb, unlike Pbx1, which is expressed only in the proximal bud. By exploiting a Pbx1/Pbx2 loss-of-function mouse model,we demonstrate that, despite the lack of limb abnormalities in Pbx2-deficient (Pbx2–/–) embryos,compound Pbx1–/–; Pbx2+/–mutants, in addition to their exacerbated proximal limb defects, exhibit novel and severe distal abnormalities. Additionally, we reveal that Pbx1–/–; Pbx2–/–embryos lack limbs altogether. Furthermore, we establish that, unlike in flies, where the leg develops independently of Hox and where the Pbx ortholog Exd is required for specification of proximal (but not distal) limbs,in vertebrates, distal limb patterning is Pbx1/Pbx2dependent. Indeed, we demonstrate that Pbx genetic requirement is mediated, at least in part, through their hierarchical control of Hox spatial distribution and Shh expression. Overall, we establish that, by controlling the spatial expression of Hox genes in the posterior limb and regulating ZPA function, Pbx1/Pbx2 exert a primary hierarchical function on Hox genes, rather than behaving merely as Hox ancillary factors.</jats:p> <i>Pbx1/Pbx2</i>requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution and<i>Shh</i>expression Development |
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| title |
Pbx1/Pbx2requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution andShhexpression |
| title_unstemmed |
Pbx1/Pbx2requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution andShhexpression |
| title_full |
Pbx1/Pbx2requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution andShhexpression |
| title_fullStr |
Pbx1/Pbx2requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution andShhexpression |
| title_full_unstemmed |
Pbx1/Pbx2requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution andShhexpression |
| title_short |
Pbx1/Pbx2requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution andShhexpression |
| title_sort |
<i>pbx1/pbx2</i>requirement for distal limb patterning is mediated by the hierarchical control of hox gene spatial distribution and<i>shh</i>expression |
| topic |
Developmental Biology Molecular Biology |
| url |
http://dx.doi.org/10.1242/dev.02395 |
| publishDate |
2006 |
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2263-2273 |
| description |
<jats:p>Vertebrate limb development occurs along three cardinal axes–proximodistal, anteroposterior and dorsoventral–that are established via the organization of signaling centers, such as the zone of polarizing activity (ZPA). Distal limb development, in turn, requires a molecular feedback loop between the ZPA expression of sonic hedgehog(Shh) and the apical ectodermal ridge. The TALE homeoprotein Pbx1 has been shown to be essential for proximal limb development. In this study, we first uncover that Pbx1 and Pbx2 are co-expressed in the lateral plate and early limb field mesoderm. Later, Pbx2 is expressed throughout the limb, unlike Pbx1, which is expressed only in the proximal bud. By exploiting a Pbx1/Pbx2 loss-of-function mouse model,we demonstrate that, despite the lack of limb abnormalities in Pbx2-deficient (Pbx2–/–) embryos,compound Pbx1–/–; Pbx2+/–mutants, in addition to their exacerbated proximal limb defects, exhibit novel and severe distal abnormalities. Additionally, we reveal that Pbx1–/–; Pbx2–/–embryos lack limbs altogether. Furthermore, we establish that, unlike in flies, where the leg develops independently of Hox and where the Pbx ortholog Exd is required for specification of proximal (but not distal) limbs,in vertebrates, distal limb patterning is Pbx1/Pbx2dependent. Indeed, we demonstrate that Pbx genetic requirement is mediated, at least in part, through their hierarchical control of Hox spatial distribution and Shh expression. Overall, we establish that, by controlling the spatial expression of Hox genes in the posterior limb and regulating ZPA function, Pbx1/Pbx2 exert a primary hierarchical function on Hox genes, rather than behaving merely as Hox ancillary factors.</jats:p> |
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| author | Capellini, Terence D., Di Giacomo, Giuseppina, Salsi, Valentina, Brendolan, Andrea, Ferretti, Elisabetta, Srivastava, Deepak, Zappavigna, Vincenzo, Selleri, Licia |
| author_facet | Capellini, Terence D., Di Giacomo, Giuseppina, Salsi, Valentina, Brendolan, Andrea, Ferretti, Elisabetta, Srivastava, Deepak, Zappavigna, Vincenzo, Selleri, Licia, Capellini, Terence D., Di Giacomo, Giuseppina, Salsi, Valentina, Brendolan, Andrea, Ferretti, Elisabetta, Srivastava, Deepak, Zappavigna, Vincenzo, Selleri, Licia |
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| description | <jats:p>Vertebrate limb development occurs along three cardinal axes–proximodistal, anteroposterior and dorsoventral–that are established via the organization of signaling centers, such as the zone of polarizing activity (ZPA). Distal limb development, in turn, requires a molecular feedback loop between the ZPA expression of sonic hedgehog(Shh) and the apical ectodermal ridge. The TALE homeoprotein Pbx1 has been shown to be essential for proximal limb development. In this study, we first uncover that Pbx1 and Pbx2 are co-expressed in the lateral plate and early limb field mesoderm. Later, Pbx2 is expressed throughout the limb, unlike Pbx1, which is expressed only in the proximal bud. By exploiting a Pbx1/Pbx2 loss-of-function mouse model,we demonstrate that, despite the lack of limb abnormalities in Pbx2-deficient (Pbx2–/–) embryos,compound Pbx1–/–; Pbx2+/–mutants, in addition to their exacerbated proximal limb defects, exhibit novel and severe distal abnormalities. Additionally, we reveal that Pbx1–/–; Pbx2–/–embryos lack limbs altogether. Furthermore, we establish that, unlike in flies, where the leg develops independently of Hox and where the Pbx ortholog Exd is required for specification of proximal (but not distal) limbs,in vertebrates, distal limb patterning is Pbx1/Pbx2dependent. Indeed, we demonstrate that Pbx genetic requirement is mediated, at least in part, through their hierarchical control of Hox spatial distribution and Shh expression. Overall, we establish that, by controlling the spatial expression of Hox genes in the posterior limb and regulating ZPA function, Pbx1/Pbx2 exert a primary hierarchical function on Hox genes, rather than behaving merely as Hox ancillary factors.</jats:p> |
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| institution | DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1 |
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| spelling | Capellini, Terence D. Di Giacomo, Giuseppina Salsi, Valentina Brendolan, Andrea Ferretti, Elisabetta Srivastava, Deepak Zappavigna, Vincenzo Selleri, Licia 1477-9129 0950-1991 The Company of Biologists Developmental Biology Molecular Biology http://dx.doi.org/10.1242/dev.02395 <jats:p>Vertebrate limb development occurs along three cardinal axes–proximodistal, anteroposterior and dorsoventral–that are established via the organization of signaling centers, such as the zone of polarizing activity (ZPA). Distal limb development, in turn, requires a molecular feedback loop between the ZPA expression of sonic hedgehog(Shh) and the apical ectodermal ridge. The TALE homeoprotein Pbx1 has been shown to be essential for proximal limb development. In this study, we first uncover that Pbx1 and Pbx2 are co-expressed in the lateral plate and early limb field mesoderm. Later, Pbx2 is expressed throughout the limb, unlike Pbx1, which is expressed only in the proximal bud. By exploiting a Pbx1/Pbx2 loss-of-function mouse model,we demonstrate that, despite the lack of limb abnormalities in Pbx2-deficient (Pbx2–/–) embryos,compound Pbx1–/–; Pbx2+/–mutants, in addition to their exacerbated proximal limb defects, exhibit novel and severe distal abnormalities. Additionally, we reveal that Pbx1–/–; Pbx2–/–embryos lack limbs altogether. Furthermore, we establish that, unlike in flies, where the leg develops independently of Hox and where the Pbx ortholog Exd is required for specification of proximal (but not distal) limbs,in vertebrates, distal limb patterning is Pbx1/Pbx2dependent. Indeed, we demonstrate that Pbx genetic requirement is mediated, at least in part, through their hierarchical control of Hox spatial distribution and Shh expression. Overall, we establish that, by controlling the spatial expression of Hox genes in the posterior limb and regulating ZPA function, Pbx1/Pbx2 exert a primary hierarchical function on Hox genes, rather than behaving merely as Hox ancillary factors.</jats:p> <i>Pbx1/Pbx2</i>requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution and<i>Shh</i>expression Development |
| spellingShingle | Capellini, Terence D., Di Giacomo, Giuseppina, Salsi, Valentina, Brendolan, Andrea, Ferretti, Elisabetta, Srivastava, Deepak, Zappavigna, Vincenzo, Selleri, Licia, Development, Pbx1/Pbx2requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution andShhexpression, Developmental Biology, Molecular Biology |
| title | Pbx1/Pbx2requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution andShhexpression |
| title_full | Pbx1/Pbx2requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution andShhexpression |
| title_fullStr | Pbx1/Pbx2requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution andShhexpression |
| title_full_unstemmed | Pbx1/Pbx2requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution andShhexpression |
| title_short | Pbx1/Pbx2requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution andShhexpression |
| title_sort | <i>pbx1/pbx2</i>requirement for distal limb patterning is mediated by the hierarchical control of hox gene spatial distribution and<i>shh</i>expression |
| title_unstemmed | Pbx1/Pbx2requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution andShhexpression |
| topic | Developmental Biology, Molecular Biology |
| url | http://dx.doi.org/10.1242/dev.02395 |