TY - JOUR
T1 - Lacrimal gland budding requires PI3K-dependent suppression of EGF signaling
AU - Wang, Qian
AU - Tao, Chenqi
AU - Hannan, Abdul
AU - Yoon, Sungtae
AU - Min, Xuanyu
AU - Peregrin, John
AU - Qu, Xiuxia
AU - Li, Hongge
AU - Yu, Honglian
AU - Zhao, Jean
AU - Zhang, Xin
N1 - Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved.
PY - 2021/6
Y1 - 2021/6
N2 - The patterning of epithelial buds is determined by the underlying signaling network. Here, we study the crosstalk 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.
AB - The patterning of epithelial buds is determined by the underlying signaling network. Here, we study the crosstalk 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.
UR - http://www.scopus.com/inward/record.url?scp=85108988907&partnerID=8YFLogxK
U2 - 10.1126/sciadv.abf1068
DO - 10.1126/sciadv.abf1068
M3 - Article
C2 - 34193412
AN - SCOPUS:85108988907
SN - 2375-2548
VL - 7
JO - Science Advances
JF - Science Advances
IS - 27
M1 - eabf1068
ER -