Publications by authors named "Randall Wakefield"
During development, morphogens pattern tissues by instructing cell fate across long distances. Directly visualizing morphogen transport in situ has been inaccessible, so the molecular mechanisms ensuring successful morphogen delivery remain unclear. To tackle this longstanding problem, we developed a mouse model for compromised sonic hedgehog (SHH) morphogen delivery and discovered that endocytic recycling promotes SHH loading into signaling filopodia called cytonemes.
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- T follicular helper (T) cells play an essential role in supporting B cell function and the immune response, with transcription factors like BCL6 driving their development.
- This study uncovers the importance of the CDP-ethanolamine pathway and specific enzymes (ETNK1, PCYT2, SELENOI) for promoting T cell differentiation by regulating the expression of the CXCR5 protein, critical for T cell response.
- The research shows that lipid metabolism, particularly through the synthesis of phosphatidylethanolamine (PE), is vital in maintaining CXCR5's presence on T cells and ensuring effective humoral immunity, indicating a link between metabolic processes and immune cell signaling.
Evidence is lacking as to how developing neurons integrate mitogenic signals with microenvironment cues to control proliferation and differentiation. We determine that the Siah2 E3 ubiquitin ligase functions in a coincidence detection circuit linking responses to the Shh mitogen and the extracellular matrix to control cerebellar granule neurons (CGN) GZ occupancy. We show that Shh signaling maintains Siah2 expression in CGN progenitors (GNPs) in a Ras/Mapk-dependent manner.
View Article and Find Full Text PDFMaintenance of epithelial cell polarity and epithelial barrier relies on the spatial organization of the actin cytoskeleton and proper positioning/assembly of intercellular junctions. However, how these processes are regulated is poorly understood. Here we reveal a key role for the multifunctional protein Alix in both processes.
View Article and Find Full Text PDFNecroptosis is a cell death pathway regulated by the receptor interacting protein kinase 3 (RIPK3) and the mixed lineage kinase domain-like (MLKL) pseudokinase. How MLKL executes plasma membrane rupture upon phosphorylation by RIPK3 remains controversial. Here, we characterize the hierarchical transduction of structural changes in MLKL that culminate in necroptosis.
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- Programmed necrosis, or necroptosis, is a type of cell death initiated by the enzyme RIPK3 and is influenced by mitochondria and reactive oxygen species (ROS).
- The study finds that cells lacking mitochondria can still undergo programmed necrosis triggered by RIPK3, even though they are resistant to apoptosis (another form of cell death).
- While the ROS scavenger BHA can delay necroptosis caused by TNF (a signaling molecule), it does not affect necroptosis linked to direct RIPK3 activation, suggesting that mitochondrial ROS is not essential for this particular cell death process.