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Notch Research

Notch signaling is essential for the balance of cilia type in the left-right Organizer (LRO). There are two types of cilia: motile and immotile. Activation of Notch leads to more immotile cilia.

The notch pathway plays an important role in cell fate decisions. In a patient with Heterotaxy, we identified an abnormality in galnt11, a glycosylation gene we showed alters LR patterning in Xenopus. Unexpectedly, loss of galnt11 also leads to an increase in the number of multicilitated cells on the epidermis of the frog embryo. The Kintner lab has elegantly shown this can be a Notch phenotype. In a series of experiments, we then showed galnt11 appears to activate the notch pathway, directly glycosylates Notch peptides, and interestingly, can enhance the cleavage of a Notch peptide spanning the juxtamembrane region of Notch. Proteolytic processing of Notch is critical for its signaling function. Finally, we demonstrated Notch is essential for specifying motile vs. immotile cilia in the Left-Right Organizer, and showed this specification is essential for establishing proper LR pattern.