The data reveal that multiple extracellular, cytoplasmic, and nuclear regulators intricately modulate Wnt signaling levels, and that receptor-ligand specificity and feedback loops help to determine WNT signaling outputs.
This work isolated active Wnt molecules, including the product of the mouse Wnt3a gene, and found the proteins to be palmitoylated on a conserved cysteine, indicating that the lipid is important for signalling.
It is concluded that the Wnt signalling pathway is critical for normal HSC homeostasis in vitro and in vivo, and insight is provided into a potential molecular hierarchy of regulation of HSC development.
Current understanding of Wnt function and signaling mechanisms is reviewed in a comparative approach, highlighting novelty and underscoring questions that remain, and putting emphasis on the latest findings.
This study shows for the first time that a single Wnt ligand can initiate discrete signaling pathways through the activation of two distinct receptors, and proposes a model wherein receptor context dictates Wnt signaling output.
Over the past two years the understanding of Wnt signaling has been substantially improved by the identification of Frizzled proteins as cell surface receptors for Wnts and by the finding that beta-catenin, a component downstream of the receptor, can translocate to the nucleus and function as a transcriptional activator.
Evidence is assembled of possible interrelations between Wnt and other growth factor signaling, beta-catenin functions, and cadherin-mediated adhesion in tissue differentiation.
It is suggested that brain IPCs are the main systemic supply of insulin during larval growth and pancreatic islet β cells are functionally analogous and may have evolved from a common ancestral insulin-producing neuron.