The improved pregnancy outcomes along with the simple and user-friendly design of the microfluidic/microfunnel system has potential to alleviate many inefficiencies in embryo production for biomedical research, genetic gain in domestic species and assisted reproductive technologies in humans.

No abstract

Longitudinal bone growth ceases with growth plate senescence during puberty. However, the molecular mechanisms of this phenomenon are largely unexplored. Here, we examined Wnt-responsive genes before and after growth plate senescence and found that CXXC finger protein 5 (CXXC5), a negative regulator of the Wnt/β-catenin pathway, was gradually elevated with reduction of Wnt/β-catenin signaling during senescent changes of rodent growth plate. Cxxc5−/− mice demonstrated delayed growth plate senescence and tibial elongation. As CXXC5 functions by interacting with dishevelled (DVL), we sought to identify small molecules capable of disrupting this interaction. In vitro screening assay monitoring CXXC5–DVL interaction revealed that several indirubin analogs were effective antagonists of this interaction. A functionally improved indirubin derivative, KY19382, elongated tibial length through delayed senescence and further activation of the growth plate in adolescent mice. Collectively, our findings reveal an important role for CXXC5 as a suppressor of longitudinal bone growth involving growth plate activity.

No abstract

RAS proteins play critical roles in various cellular processes, including growth and transformation. RAS proteins are subjected to protein stability regulation via the Wnt/β‐catenin pathway, and glycogen synthase kinase 3 beta (GSK3β) is a key player for the phosphorylation‐dependent RAS degradation through proteasomes. GSK3β‐mediated RAS degradation does not occur in cells that express a nondegradable mutant (MT) β‐catenin. Here, we show that β‐catenin directly interacts with RAS at the α‐interface region that contains the GSK3β phosphorylation sites, threonine 144 and threonine 148 residues. Exposure of these sites by prior β‐catenin degradation is required for RAS degradation. The introduction of a peptide that blocks the β‐catenin‐RAS interaction by binding to β‐catenin rescues the GSK3β‐mediated RAS degradation in colorectal cancer (CRC) cells that express MT β‐catenin. The coregulation of β‐catenin and RAS stabilities by the modulation of their interaction provides a mechanism for Wnt/β‐catenin and RAS‐ERK pathway cross‐talk and the synergistic transformation of CRC by both APC and KRAS mutations.