Amot and Yap1 regulate neuronal dendritic tree complexity and locomotor coordination in mice

Area of Science:

• Neuroscience
• Cell Biology
• Developmental Biology

Background:

• The angiomotin (Amot)-Yes-associated protein 1 (Yap1) complex regulates cell contact, polarity, and growth.
• The specific roles of Amot and Yap1 in the central nervous system are not well understood.

Purpose of the Study:

• To investigate the function of Amot and Yap1 in neuronal development, particularly dendritic morphogenesis.
• To elucidate the molecular mechanisms underlying Amot and Yap1's role in dendrite growth.

Main Methods:

• Utilized cultured hippocampal cells and Purkinje cells.
• Performed conditional deletion of Amot and Yap1 in neurons.
• Analyzed dendritic complexity, cerebellar morphology, and motor coordination.

Main Results:

• Amot mediates dendritic morphogenesis in hippocampal and Purkinje cells.
• Amot and Yap1 interaction is essential for dendrite growth and arborization.
• Conditional deletion of Amot and Yap1 resulted in reduced dendritic complexity, abnormal cerebellar morphology, and motor deficits.
• Amot/Yap1 function in dendrite development is independent of TEAD transcription factors and Hippo pathway genes.
• Amot and Yap1 regulate dendrite development via phosphorylation of S6 kinase and S6 ribosomal protein.

Conclusions:

• Amot and Yap1 are critical for proper dendritic development and cerebellar structure.
• The Amot-Yap1 complex influences motor coordination through its role in neuronal development.
• This pathway regulates dendrite growth independent of canonical Hippo pathway signaling, acting through S6 kinase phosphorylation.