Signaling by the Wnt family of secreted glycoproteins plays important roles in embryonic development and adult homeostasis Wnt signaling is modulated by a number of evolutionarily conserved inhibitors and activators Wnt inhibitors belong to small protein families, including sFRP, Dkk, WIF, Wise/SOST, Cerberus, IGFBP, Shisa, Waif1, APCDD1, and Tiki1 Their common feature is to antagonize Wnt signaling by preventing ligand-receptor interactions or Wnt receptor maturation Conversely, the Wnt activators, R-spondin and Norrin, promote Wnt signaling by binding to Wnt receptors or releasing a Wnt-inhibitory step With few exceptions, these antagonists and agonists are not pure Wnt modulators, but also affect additional signaling pathways, such as TGF-β and FGF signaling Here we discuss their interactions with Wnt ligands and Wnt receptors, their role in developmental processes, as well as their implication in disease

/pdf/secreted-and-transmembrane-wnt-inhibitors-and-activators-25a40nvfuh.pdf

Secreted and Transmembrane Wnt Inhibitors and Activators

Although motor deficits are gaining attention in autism research much less attention has been paid to the physical activity patterns in this group of children. The participants in this study were a group of children with autism spectrum disorder (N = 72) between the ages of 9-18 years. This cross-sectional study explored the physical activity patterns of seventy-two children with autism spectrum disorder as they aged. Results indicated significant differences between the mean time spent in moderate to vigorous physical activity and the mean time spent in sedentary activity. Older children with autism spectrum disorder are significantly more physically inactive, compared to younger children. Physical activity programs and interventions need to address this deficit, in physical activity. Children with autism have a similar trend in physical activity patterns compared to their peers without autism; associated benefits and future research will be discussed.

/pdf/the-physical-activity-patterns-of-children-with-autism-3gm6jyfvrr.pdf

The physical activity patterns of children with autism

Comprehensive expression analysis of all Wnt genes and their major secreted antagonists during mouse limb development and cartilage differentiation.

Follistatin-like 1 (FSTL1) is a secreted glycoprotein displaying expression changes during development and disease, among which cardiovascular disease, cancer, and arthritis. The cardioprotective role of FSTL1 has been intensively studied over the last years, though its mechanism of action remains elusive. FSTL1 is involved in multiple signaling pathways and biological processes, including vascularization and regulation of the immune response, a feature that complicates its study. Binding to the DIP2A, TLR4 and BMP receptors have been shown, but other molecular partners probably exist. During cancer progression and rheumatoid arthritis, controversial data have been reported with respect to the proliferative, apoptotic, migratory, and inflammatory effects of FSTL1. This controversy might reside in the extensive post-transcriptional regulation of FSTL1. The FSTL1 primary transcript also encodes for a microRNA (miR-198) in primates and multiple microRNA-binding sites are present in the 3′UTR. The switch between expression of the FSTL1 protein and miR-198 is an important regulator of tumour metastasis and wound healing. The glycosylation state of FSTL1 is a determinant of biological activity, in cardiomyocytes the glycosylated form promoting proliferation and the non-glycosylated working anti-apoptotic. Moreover, the glycosylation state shows differences between species and tissues which might underlie the differences observed in in vitro studies. Finally, regulation at the level of protein secretion has been described.

/pdf/follistatin-like-1-in-development-and-human-diseases-798km3pggq.pdf

Follistatin-like 1 in development and human diseases.

Wnt is a complex signaling pathway involved in the regulation of crucial biological functions such as development, proliferation, differentiation and migration of cells, mainly stem cells, which are virtually present in all embryonic and adult tissues. Conversely, dysregulation of Wnt signal is implicated in development/progression/invasiveness of different kinds of tumors, wherein a certain number of multipotent cells, namely "cancer stem cells", are characterized by high self-renewal and aggressiveness. Hence, the pharmacological modulation of Wnt pathway could be of particular interest, especially in tumors for which the current standard therapy results to be unsuccessful. This might be the case of glioblastoma multiforme (GBM), one of the most lethal, aggressive and recurrent brain cancers, probably due to the presence of highly malignant GBM stem cells (GSCs) as well as to a dysregulation of Wnt system. By examining the most recent literature, here we point out several factors in the Wnt pathway that are altered in human GBM and derived GSCs, as well as new molecular strategies or experimental drugs able to modulate/inhibit aberrant Wnt signal. Altogether, these aspects serve to emphasize the existence of alternative pharmacological targets that may be useful to develop novel therapies for GBM.

https://www.mdpi.com/2073-4425/9/2/105/pdf

The Role of Wnt Signal in Glioblastoma Development and Progression: A Possible New Pharmacological Target for the Therapy of This Tumor

Expression pattern of Wnt inhibitor factor 1(Wif1) during the development in mouse CNS.

Expression of Frizzled10 in mouse central nervous system.

Background
The rodent barrel cortex has been established as an ideal model for studying the development and plasticity of a neuronal circuit. The barrel cortex consists of barrel and septa columns, which receive various input signals through distinct pathways. The lemniscal pathway transmits whisker-specific signals to homologous barrel columns, and the paralemniscal pathway transmits multi-whisker signals to both barrel and septa columns. The integration of information from both lemniscal and paralemniscal pathways in the barrel cortex is critical for precise object recognition. As the main target of the posterior medial nucleus (POm) in the paralemniscal pathway, layer 5a (L5a) pyramidal neurons are involved in both barrel and septa circuits and are considered an important site of information integration. However, information on L5a neurons is very limited. This study aims to explore the cellular features of L5a neurons and to provide a morphological basis for studying their roles in the development of the paralemniscal pathway and in information integration.

/pdf/calretinin-positive-l5a-pyramidal-neurons-in-the-development-1ksiguvyfj.pdf

Calretinin-positive L5a pyramidal neurons in the development of the paralemniscal pathway in the barrel cortex

The expression pattern of Follistatin-like 1 in mouse central nervous system development.

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Papers

Expression pattern of Wnt inhibitor factor 1(Wif1) during the development in mouse CNS.

Expression of Frizzled10 in mouse central nervous system.

Calretinin-positive L5a pyramidal neurons in the development of the paralemniscal pathway in the barrel cortex

The expression pattern of Follistatin-like 1 in mouse central nervous system development.