Developmental origins of species-specific muscle pattern

Vertebrate jaw muscle anatomy is conspicuously diverse but developmental processes that generate such variation remain relatively obscure. To identify mechanisms that produce species-specific jaw muscle pattern we conducted transplant experiments using Japanese quail and White Pekin duck, which exhibit considerably different jaw morphologies in association with their particular modes of feeding. Previous work indicates that cranial muscle formation requires interactions with adjacent skeletal and muscular connective tissues, which arise from neural crest mesenchyme. We transplanted neural crest mesenchyme from quail to duck embryos, to test if quail donor-derived skeletal and muscular connective tissues could confer species-specific identity to duck host jaw muscles. Our results show that duck host jaw muscles acquire quail-like shape and attachment sites due to the presence of quail donor neural crest-derived skeletal and muscular connective tissues. Further, we find that these species-specific transformations are preceded by spatiotemporal changes in expression of genes within skeletal and muscular connective tissues including Sox9, Runx2, Scx, and Tcf4, but not by alterations to histogenic or molecular programs underlying muscle differentiation or specification. Thus, neural crest mesenchyme plays an essential role in generating species-specific jaw muscle pattern and in promoting structural and functional integration of the musculoskeletal system during evolution.     

Wnt/β-catenin/Tcf Signaling Pathway Activation in Malignant Progression of Rat Gliomas Induced by Transplacental <Emphasis Type="Italic">N-</Emphasis>Ethyl-<Emphasis Type="Italic">N-</Emphasis>Nitrosourea Exposure

Although Wnt/β-catenin/Tcf signaling pathway has been shown to be a crucial factor in the development of many cancers, little is known about its role in glioma malignancy. In the present study, we report the first evidence that Wnt/β-catenin/Tcf signaling pathway is constitutively activated in experimental gliomas induced by single transplacental dose of N-ethyl-N-nitrosourea (ENU). In the present study we analyzed ENU induced rat gliomas of different stages (P90, P135 and P180) for the expression of β-catenin, Lef1, Tcf4 and their targets c-Myc, N-Myc and cyclin D1. Western blot analysis revealed upregulation of β-catenin, Lef1, Tcf4, c-Myc, N-Myc and cyclin D1 in gliomas compared to controls and their levels were progressively increased from initial stage (P90) to progression stage (P180). In consistent with this, immunohistochemistry revealed the cytoplasmic and nuclear accumulation of β-catenin, and nuclear positivity was evident for Lef1, Tcf4, c-Myc, N-Myc and cyclin D1. Based on these results, we conclude that Wnt/β-catenin pathway may play a major role in the tumorigenesis and tumor progression in ENU induced rat gliomas.     

Update on Wnt signaling in bone cell biology and bone disease

For more than a decade, Wnt signaling pathways have been the focus of intense research activity in bone biology laboratories because of their importance in skeletal development, bone mass maintenance, and therapeutic potential for regenerative medicine. It is evident that even subtle alterations in the intensity, amplitude, location, and duration of Wnt signaling pathways affects skeletal development, as well as bone remodeling, regeneration, and repair during a lifespan. Here we review recent advances and discrepancies in how Wnt/Lrp5 signaling regulates osteoblasts and osteocytes, introduce new players in Wnt signaling pathways that have important roles in bone development, discuss emerging areas such as the role of Wnt signaling in osteoclastogenesis, and summarize progress made in translating basic studies to clinical therapeutics and diagnostics centered around inhibiting Wnt pathway antagonists, such as sclerostin, Dkk1 and Sfrp1. Emphasis is placed on the plethora of genetic studies in mouse models and genome wide association studies that reveal the requirement for and crucial roles of Wnt pathway components during skeletal development and disease.     

Suppression of Tcf1 by Inflammatory Cytokines Facilitates Effector CD8 T Cell Differentiation

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