Sp6 and Sp8 Transcription Factors Control AER Formation and Dorsal-Ventral Patterning in Limb Development
In this report we examined the functional roles of Sp6 and Sp8 during limb development using compound loss-of-function mutants. Sp6 and Sp8, two members of the Sp gene family, are expressed in the limb bud ectoderm and function downstream of WNT/βcatenin signaling for Fgf8 induction. The analysis of the allelic series shows that the progressive reduction in the dose of Sp6 and Sp8 gene products leads to predictable morphology, from syndactyly, to split hand/foot malformation, oligodactyly, truncation and finally amelia, indicating that these two factors act in a complementary manner. The molecular characterization of the mutant limbs reveal that Sp6/Sp8 are required in a dose-dependent manner for Fgf8 and En1 induction, thereby placing them as an important link between the induction of the AER and the establishment of dorsal-ventral patterning during limb development.
Vyšlo v časopise:
Sp6 and Sp8 Transcription Factors Control AER Formation and Dorsal-Ventral Patterning in Limb Development. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004468
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1004468
Souhrn
In this report we examined the functional roles of Sp6 and Sp8 during limb development using compound loss-of-function mutants. Sp6 and Sp8, two members of the Sp gene family, are expressed in the limb bud ectoderm and function downstream of WNT/βcatenin signaling for Fgf8 induction. The analysis of the allelic series shows that the progressive reduction in the dose of Sp6 and Sp8 gene products leads to predictable morphology, from syndactyly, to split hand/foot malformation, oligodactyly, truncation and finally amelia, indicating that these two factors act in a complementary manner. The molecular characterization of the mutant limbs reveal that Sp6/Sp8 are required in a dose-dependent manner for Fgf8 and En1 induction, thereby placing them as an important link between the induction of the AER and the establishment of dorsal-ventral patterning during limb development.
Zdroje
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Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
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