Mesodermal fate decisions of a stem cell: the Wnt switch

Stem cells are a powerful resource for cell-based transplantation therapies in osteodegenerative disorders, but before some kinds of stem cells can be applied clinically, several aspects of their expansion and differentiation need to be better controlled. Wnt molecules and members of the Wnt signaling cascade have been ascribed a role in both these processes in vitro as well as normal development in vivo. However some results are controversial. In this review we will present the hypothesis that both canonical and non-canonical signaling are involved in mesenchymal cell fate regulation, such as adipogenesis, chondrogenesis and osteogenesis, and that in vitro it is a timely switch between the two that specifies the identity of the differentiating cell. We will specifically focus on the in vitro differentiation of adipocytes, chondrocytes and osteoblasts contrasting embryonic and mesenchymal stem cells as well as the role of Wnts in mesenchymal fate specification during embryogenesis

Townes-Brocks syndrome: twenty novel SALL1 mutations in sporadic and familial cases and refinement of the SALL1 hot spot region

Townes-Brocks syndrome (TBS) is an autosomal dominant malformation syndrome characterized by renal, anal, ear, and thumb anomalies caused by SALL1 mutations. To date, 36 SALL1 mutations have been described in TBS patients. All but three of those, namely p.R276X, p.S372X, and c.1404dupG, have been found only in single families thereby preventing phenotype-genotype correlations. Here we present 20 novel mutations (12 short deletions, five short duplications, three nonsense mutations) in 20 unrelated families. We delineate the phenotypes and report previously unknown ocular manifestations, i.e. congenital cataracts with unilateral microphthalmia. We show that 46 out of the now 56 SALL1 mutations are located between the coding regions for the glutamine-rich domain mediating SALL protein interactions and 65 bp 3\u27 of the coding region for the first double zinc finger domain, narrowing the SALL1 mutational hotspot region to a stretch of 802 bp within exon 2. Of note, only two SALL1 mutations would result in truncated proteins without the glutamine-rich domain, one of which is reported here. The latter is associated with anal, ear, hand, and renal manifestations, indicating that the glutamine-rich domain is not required for typical TBS