A role for Zic1 and Zic2 in Myf5 regulation and somite myogenesis

Abstract

Zic genes encode a conserved family of zinc finger proteins with essential functions in neural development and axial skeletal patterning in the vertebrate embryo. Zic proteins also function as Gli co-factors in Hedgehog signaling. Here, we report that Zic genes have a role in Myf5 regulation for epaxial somite myogenesis in the mouse embryo. In situ hybridization studies show that Zic1, 2, and 3 transcripts are expressed in Myf5-expressing epaxial myogenic progenitors in the dorsal medial dermomyotome of newly forming somites, and immunohistological studies show that Zic2 protein is co-localized with Myf5 and Pax3 in the dorsal medial lip of the dermomyotome, but is not expressed in the forming myotome. In functional reporter assays, Zic1 and Zic2, but not Zic3, potentiate the transactivation of Gli-dependent Myf5 epaxial somite-specific (ES) enhancer activity in 3T3 cells, and Zic1 activates endogenous Myf5 expression in 10T1/2 cells and in presomitic mesoderm explants. Zic2 also co-immunoprecipitates with Gli2, indicating that Zic2 forms complexes with Gli2 to promote Myf5 expression. Genetic studies show that, although Zic2 and Zic1 are activated normally in Sonic Hedgehog−/− mutant embryos, Myf5 expression in newly forming somites is deficient in both Sonic Hedgehog−/− and in Zic2kd/kd mutant mouse embryos, providing further evidence that these Zic genes are upstream regulators of Hedgehog-mediated Myf5 activation. Myf5 activation in newly forming somites is delayed in Zic2 mutant embryos until the time of Zic1 activation, and both Zic2 and Myf5 require Noggin for their activation.

A stringent validation of mouse adipose tissue identity markers

“…In all the primary cell cultures [BA (brown adipocytes), ingWA (inguinal white adipocytes), and eWA (epididymal white adipocytes)], Ucp1 expression was induced by NE and rosiglitazone treatment, in accord with earlier studies (Fig. 1B) (26,28,40). In cultured brown adipocytes (BA), Ucp1 was increased to similar mRNA levels in the presence of acute NE or of chronic rosiglitazone (Fig.…”

“…Encircled points were excluded from the analysis. expression of Zic1 is in line with its expression during embryonic development, which is restricted to the most anterior somites (26). This anatomic restriction of Zic1 expression can also explain its absence in mBAT and prBAT, as these are the most posterior BAT(-like) depots (Fig.…”

“…14C). This is not completely unexpected, as Zic1 expression during embryonic development is restricted to the most anterior somites (26). Indeed, there is a sharp boundary between neural crest-derived and mesodermderived tissues at the level of the clavicle (20), and Zic1 expression may thus be related to this difference in origin of the tissues.…”

Zebrafish zic2 controls formation of periocular neural crest and choroid fissure morphogenesis

“…This analysis identified myotome/somite, craniofacial elements, and heart (enrichment scores 2.78, 2.24 and 1.71, respectively). Myotome/somite markers and heart markers were found primarily in the upregulated set, consistent with expression of zic2b in zebrafish somites (Toyama et al, 2004) and with the demonstrated function for mammalian Zic2 during myogenesis (Inoue et al, 2007; Pan et al, 2011). In contrast, craniofacial markers appeared among transcripts depleted in zic2 mutants.…”

Modular development of the teleost trunk along the dorsoventral axis and zic1/zic4 as selector genes in the dorsal module

“…In particular, zic1/zic4 have been well investigated in the context of neural development (Aruga et al, 2002;Elsen et al, 2008;Grinberg et al, 2004). However, despite previous descriptions of skeletal and muscular defects in the mouse Zic1 mutants (Aruga et al, 1999;Pan et al, 2011), the role of zic1/zic4 in somite-derived tissues had remained largely unknown. In this study, we took advantage of the medaka Da mutant, an enhancer mutant for zic1/zic4, and have provided experimental evidence that the dorsal characteristics of the fish trunk, such as fin, body shape and pigmentation pattern, are orchestrated by Zic1/Zic4 in the somite.…”