The glial cells missing (gcm) regulatory gene of the sea urchin Strongylocentrotus purpuratus is first expressed in veg2 daughter cells as the genomic target of late cleavage stage Delta-Notch signaling from the skeletogenic mesoderm precursors. Gcm is required in veg2 progeny during late cleavages for the early phase of pigment cell precursor specification. Here we report on a later acting cis...

TP53 is mutated in 50% of all cancers, and its function is often compromised in cancers where it is not mutated. Here we demonstrate that the pro-tumorigenic/metastatic Six1 homeoprotein decreases p53 levels through a mechanism that does not involve the negative regulator of p53, MDM2. Instead, Six1 regulates p53 via a dual mechanism involving upregulation of microRNA-27a and downregulation of ...

PURPOSE To determine the prognostic value of the expression of Ezrin, CD44 and Six1 genes in osteosarcoma tissues of Chinese patients. METHODS Fluorescent quantitative real-time PCR was applied to study the mRNA levels of Ezrin, CD44 and Six1 genes in 32 osteosarcoma patient samples and 10 adjacent normal tissues and MG63 osteosarcoma cell lines. The analysis of relationships between pulmonar...

Branchio-oto-renal syndrome, a phenotype consisting of hearing loss, auricular malformations, branchial arch remnants, and renal anomalies is now recognized as one of the more common forms of autosomal dominant syndromic hearing impairment. Three loci known to be associated with the BOR phenotype have been identified and two genes that act in a regulatory network have been cloned, EYA1 and SIX1...

In mammals, several genetic pathways have been characterized that govern engagement of multipotent embryonic progenitors into the myogenic program through the control of the key myogenic regulatory gene Myod. Here we demonstrate the involvement of Six homeoproteins. We first targeted into a Pax3 allele a sequence encoding a negative form of Six4 that binds DNA but cannot interact with essential...

Myf5, a member of the myogenic regulatory factor family, plays a major role in determining myogenic cell fate at the onset of skeletal muscle formation in the embryo. Spatiotemporal control of its expression during development requires multiple enhancer elements spread over >100 kb at the Myf5 locus. Transcription in embryonic limbs is regulated by a 145-bp element located at -57.5 kb from the ...

In mammals, Six5, Six4 and Six1 genes are co-expressed during mouse myogenesis. Six4 and Six5 single knockout (KO) mice have no developmental defects, while Six1 KO mice die at birth and show multiple organ developmental defects. We have generated Six1Six4 double KO mice and show an aggravation of the phenotype previously reported for the single Six1 KO. Six1Six4 double KO mice are characterize...

Fewer than 30% of patients with hepatocellular carcinoma (HCC) are eligible to receive curative therapies, and so a better understanding of the molecular mechanisms of HCC is needed to identify potential therapeutic targets. The role of microRNA (miRNA) in modulating tumour progression has been demonstrated, and therapies targeting miRNA appear promising. miR-204-5p has been shown to function i...

Homeobox (Hox) genes encode transcription factors that act as critical regulators of growth and differentiation during embryogenesis. While many studies have identified increased expression of Hox genes in tumors, much less is known about the mechanistic basis by which Hox genes facilitate tumor development. In this issue of the JCI, McCoy and colleagues show that transgenic mice that express t...