Wnt Signaling Pathway in Development

Wnt Signaling Pathway

• The Wnt pathway consists of a family of ligands with homology to wingless in Drosophila
• Wnts can bind to multiple receptor complexes, triggering various downstream signaling cascades, including canonical WNT/β-catenin, non-canonical WNT/planar cell polarity (PCP), and WNT/Ca2+ pathways
• Mis-regulation of the Wnt signaling cascade can lead to eye malformations and disease

Canonical Wnt Signaling in Eye Development

• Canonical Wnt signaling plays important roles in patterning of ocular tissue, differentiation of retinal pigment epithelium, and morphogenesis of the optic cup

Disheveled (DVL) Proteins

• Disheveled proteins are a group of core intracellular effectors of the Wnt pathway
• There are three DVL proteins in vertebrates, each with specific roles depending on tissue distribution and interactions
• Mutations in DVL genes can cause human congenital disease

PTK7 in Wnt Signaling

• PTK7 (protein tyrosine kinase 7) is a transmembrane receptor that fine-tunes the Wnt signaling network
• PTK7 regulates cell polarity, cell movements, and migration, which are essential for development and disease, particularly in cancer and metastasis

Notch Signaling Pathway

• Notch is a transmembrane protein that mediates juxtacrine cell-cell communication
• Notch has multiple functions in organ formation and adult homeostasis, including cell determination and stem cell maintenance
• Notch is involved in somitogenesis and regulation of the turnover of Notch intracellular domain (NICD)

Regulation of Signaling Pathways

• Signaling pathways require termination of activation and resetting of components to allow cells to become competent again
• Multiple mechanisms of regulation exist, including positive and negative feedback loops, to fine-tune signaling pathways
• Crosstalk between signaling pathways allows cells to respond differently to the same signal, producing diverse cellular behaviors

BMP Antagonist Noggin in Skeletal Development

• The BMP antagonist Noggin sensitizes cells and potentiates the activation of non-canonical Wnt signaling in skeletal development
• There is a genetic interaction between the BMP and Wnt pathways, involved in human congenital malformations

Fgf Signaling in Spinal Cord Development

• Fgf signaling plays multiple roles in the developing spinal cord
• Fgf signaling is involved in essential processes such as neurogenesis, ventral patterning, and neural crest specification during spinal cord formation