Sox5 Is a DNA-Binding Cofactor for BMP R-Smads that Directs Target Specificity during Patterning of the Early Ectoderm

Abstract

SUMMARY The SoxD factor, Sox5, is expressed in ectodermal cells at times and places where BMP signaling is active, including the cells of the animal hemisphere at blastula stages, and the neural plate border (NPB) and neural crest (NC) at neurula stages. Sox5 is required for proper ectoderm development, and deficient embryos display patterning defects characteristic of perturbations of BMP signaling, including loss of neural crest and epidermis and expansion of the neural plate. We show that Sox5 is essential for activation of BMP target genes in embryos and explants, that it physically interacts with BMP R-Smads, and that it is essential for recruitment of Smad1/4 to BMP regulatory elements. Our findings identify Sox5 as the long sought DNA binding partner for BMP R-Smads essential to plasticity and pattern in the early ectoderm.

A pathway to bone: signaling molecules and transcription factors involved in chondrocyte development and maturation

“…Smad1, Smad5 and Smad8) in chondrocytes leads to severe chondrodysplasia (Retting et al, 2009), indicating that BMP signaling is necessary not only for the initiation of chondrogenesis but also for the maintenance of this differentiation program. Recently, BMP-regulated Smads were demonstrated to regulate gene expression in early Xenopus embryos via interaction with Sox5 (Nordin and Labonne, 2014). This study demonstrated that both Sox5 and Sox6 could bind to Smad1 (Nordin and Labonne, 2014), so it seems plausible that these transcription factors may also transduce BMP signals to activate chondrogenic differentiation.…”

“…Recently, BMP-regulated Smads were demonstrated to regulate gene expression in early Xenopus embryos via interaction with Sox5 (Nordin and Labonne, 2014). This study demonstrated that both Sox5 and Sox6 could bind to Smad1 (Nordin and Labonne, 2014), so it seems plausible that these transcription factors may also transduce BMP signals to activate chondrogenic differentiation. Lyons and colleagues noted that the chondrocyte-specific knockout of Bmpr1a and Bmpr1b resulted in both defective maturation of chondrocytes, from a resting to a columnar proliferating state, and in an inability of hypertrophic chondrocytes to complete terminal differentiation (Yoon et al, 2006).…”

Signaling pathways and tissue interactions in neural plate border formation

“…16 However, both direct Wnt/b-Catenin target genes, tfap2a and gbx2, are already expressed at that stage and in the case of tfap2a this early expression also depends on BMP signaling. 30,32,38 Moreover, tfap2a induction in na€ ıve ectodermal explants required only low levels of Wnt/ b-Catenin activity, 30 suggesting that low endogenous activity is sufficient to induce tfap2a in the NPB. During gastrulation, NPB genes apparently exhibit differential sensitivity toward Wnt/b-Catenin signaling.…”

“…30 In blastula and early gastrula stage Xenopus embryos, tfap2a is expressed in the entire non-neural ectoderm and the prospective NPB territory and a recent study showed that this expression depends on BMP activity. 31,32 The source of BMP ligands is likely the non-neural ectoderm or the prospective NPB ectoderm itself, which expresses BMP ligands in zebrafish, frog, chick and mouse embryos. 28,[33][34][35] Consistently, the potential of epidermis to induce NPB or NC is supposedly attributable to the expression of BMP ligands.…”

Tissue specific regulation of the chick Sox10E1 enhancer by different Sox family members

“…A potential candidate for binding to the M4 site is the SoxD family member, Sox5, previously implicated in cranial neural crest formation in chick and Xenopus (Perez-Alcala et al, 2004, Nordin and LaBonne, 2014). Consistent with previous reports (Perez-Alcala et al, 2004), we observed Sox5 expression as early as stage HH7 in the forming cranial neural folds and its expression becomes more pronounced when neural crest cells arise at stage HH9-10.…”