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Lacrimal gland budding requires PI3K-dependent suppression of EGF signaling.

Science advances | 2021

The patterning of epithelial buds is determined by the underlying signaling network. Here, we study the cross-talk between phosphoinositide 3-kinase (PI3K) and Ras signaling during lacrimal gland budding morphogenesis. Our results show that PI3K is activated by both the p85-mediated insulin-like growth factor (IGF) and Ras-mediated fibroblast growth factor (FGF) signaling. On the other hand, PI3K also promotes extracellular signal-regulated kinase (ERK) signaling via a direct interaction with Ras. Both PI3K and ERK are upstream regulators of mammalian target of rapamycin (mTOR), and, together, they prevent expansion of epidermal growth factor (EGF) receptor expression from the lacrimal gland stalk to the bud region. We further show that this suppression of EGF signaling is necessary for induction of lacrimal gland buds. These results reveal that the interplay between PI3K, mitogen-activated protein kinase, and mTOR mediates the cross-talk among FGF, IGF, and EGF signaling in support of lacrimal gland development.

Pubmed ID: 34193412 RIS Download

Associated grants

  • Agency: NEI NIH HHS, United States
    Id: K99 EY032171
  • Agency: NCI NIH HHS, United States
    Id: P50 CA168504
  • Agency: NEI NIH HHS, United States
    Id: P30 EY019007
  • Agency: NEI NIH HHS, United States
    Id: R01 EY018868
  • Agency: NEI NIH HHS, United States
    Id: R01 EY031210

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