XSIP1 is essential for early neural gene expression and neural differentiation by suppression of BMP signaling

Abstract

Neural differentiation is induced by inhibition of BMP signaling. Secreted inhibitors of BMP such as Chordin from the Spemann organizer contribute to the initial step of neural induction. Xenopus Smad-interacting protein-1 gene (XSIP1) is expressed in neuroectoderm from the early gastrula stage through to the neurula stage. XSIP1 is able to inhibit BMP signaling and overexpression of XSIP1 induces neural differentiation. To clarify the function of XSIP1 in neural differentiation, we performed a loss-of-function study of XSIP1. Knockdown of XSIP1 inhibited SoxD expression and neural differentiation. These results indicate that XSIP1 is essential for neural induction. Furthermore, loss-of-function experiments showed that SoxD is essential for XSIP1 transcription and for neural differentiation. However, inhibition of XSIP1 translation prevented neural differentiation induced by SoxD; thus, SoxD was not sufficient to mediate neural differentiation. Expression of XSIP1 was also required for inhibition of BMP signaling. Together, these results suggest that XSIP1 and SoxD interdependently function to maintain neural differentiation.

Embryonic Neural Inducing Factor Churchill Is not a DNA-binding Zinc Finger Protein: Solution Structure Reveals a Solvent-exposed β-Sheet and Zinc Binuclear Cluster

“…14 The specific role of ChCh appears to be to up-regulate the Smad-interacting protein1 (Sip1), 14 which is an essential protein in neural induction. 46 Suppression of ChCh expression results in abrogation of Sip1 expression and an observable decrease in the development of a neural plate in the chick embryo, implying that Sip1 is a direct regulatory target of ChCh. Based on these findings, it was proposed that ChCh is a key factor in the cellular decision to adopt a mesodermal or neural fate, exerted through the actions of its regulatory target gene Sip1.…”

Complementary expression pattern of Zfhx1 genes Sip1 and δEF1 in the mouse embryo and their genetic interaction revealed by compound mutants

“…In this study, two related Zfhx1 transcription factors in mouse encoded by Zfhx1a (␦EF1) (Funahashi et al, 1993) and Zfhx1b (Sip1) (Verschuren et al, 1999;Zeb2, Postigo and Dean, 2000) genes (the Zfhx1 gene family) were investigated. Zfhx1 genes, named after Drosophila Zfh1 (Fortini et al, 1991), are conserved among animal species from nematode to higher vertebrates (Genetta and Kadesch, 1996;Sekido et al, 1996;Wakamatsu et al, 2001;Papin et al, 2002, Wacker et al, 2003Nitta et al, 2004), indicating an evolutionarily conserved important regulatory function. Protein factors in this family are characterized by the possession of a pair of similar zinc finger clusters near the N-and C-termini, and a homeodomain in the middle.…”

δEF1 and SIP1 are differentially expressed and have overlapping activities duringXenopusembryogenesis

“…We and others have found that Xenopus SIP1 (XSIP1) is expressed in the early embryo in the neurectoderm and plays a role in neural differentiation (Eisaki et al, 2000;van Grunsven et al, 2000;Nitta et al, 2004). In this manuscript, we wanted to know whether SIP1 and ␦EF1 have overlapping, counteracting, or distinct functions in the regulation of early embryogenesis.…”

“…Injection of RNA encoding XSIP1 or human SIP1 in blastomeres of one-to four-cell stage Xenopus embryos has been shown to cause repression of Xbra in the mesoderm and of the ectodermal marker epidermal keratin (EK), and induction of the neural plate marker Sox2, a gene critical for early neurogenesis (Papin et al, 2002;Nitta et al, 2004). To determine whether X␦EF1 has transcription regulatory effects similar to XSIP1 in this type of experiments, we injected RNA encoding a myc-tagged X␦EF1 or XSIP1 into Xenopus embryos (250 -500 pg RNA).…”

“…Overproduction of XSIP1 induces neural-specific gene expression in explants of ectoderm and represses in the embryo the transcription of the pan-mesodermal and nodal-induced brachyury (Xbra) gene, of BMP4, and of other genes in the presumptive epidermis (Eisaki et al, 2000;Lerchner et al, 2000;Papin et al, 2002;Postigo et al, 2003). Loss-of-function studies in Xenopus showed that XSIP1 is essential for neural induction in amphibian embryos (Nitta et al, 2004).…”