PMID- 34193412
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220521
IS  - 2375-2548 (Electronic)
IS  - 2375-2548 (Linking)
VI  - 7
IP  - 27
DP  - 2021 Jun
TI  - Lacrimal gland budding requires PI3K-dependent suppression of EGF signaling.
LID - 10.1126/sciadv.abf1068 [doi]
LID - eabf1068
AB  - 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.
CI  - Copyright (c) 2021 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 
      (CC BY-NC).
FAU - Wang, Qian
AU  - Wang Q
AUID- ORCID: 0000-0002-6166-3081
AD  - Departments of Ophthalmology, Pathology, and Cell Biology, Columbia University, 
      New York, NY, USA.
FAU - Tao, Chenqi
AU  - Tao C
AUID- ORCID: 0000-0002-4346-7343
AD  - Departments of Ophthalmology, Pathology, and Cell Biology, Columbia University, 
      New York, NY, USA.
FAU - Hannan, Abdul
AU  - Hannan A
AD  - Departments of Ophthalmology, Pathology, and Cell Biology, Columbia University, 
      New York, NY, USA.
FAU - Yoon, Sungtae
AU  - Yoon S
AUID- ORCID: 0000-0001-6422-5047
AD  - Departments of Ophthalmology, Pathology, and Cell Biology, Columbia University, 
      New York, NY, USA.
FAU - Min, Xuanyu
AU  - Min X
AD  - Departments of Ophthalmology, Pathology, and Cell Biology, Columbia University, 
      New York, NY, USA.
FAU - Peregrin, John
AU  - Peregrin J
AUID- ORCID: 0000-0001-6174-7026
AD  - Departments of Ophthalmology, Pathology, and Cell Biology, Columbia University, 
      New York, NY, USA.
FAU - Qu, Xiuxia
AU  - Qu X
AUID- ORCID: 0000-0002-9496-4809
AD  - Wuxi School of Medicine, Jiangnan University, Wuxi, China.
FAU - Li, Hongge
AU  - Li H
AD  - Departments of Ophthalmology, Pathology, and Cell Biology, Columbia University, 
      New York, NY, USA.
FAU - Yu, Honglian
AU  - Yu H
AD  - Departments of Ophthalmology, Pathology, and Cell Biology, Columbia University, 
      New York, NY, USA.
AD  - Department of Biochemistry, School of Basic Medicine, Jining Medical University, 
      Jining, Shandong, China.
FAU - Zhao, Jean
AU  - Zhao J
AUID- ORCID: 0000-0002-4561-5688
AD  - Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Zhang, Xin
AU  - Zhang X
AUID- ORCID: 0000-0001-5555-0825
AD  - Departments of Ophthalmology, Pathology, and Cell Biology, Columbia University, 
      New York, NY, USA. xz2369@columbia.edu.
LA  - eng
GR  - K99 EY032171/EY/NEI NIH HHS/United States
GR  - P50 CA168504/CA/NCI NIH HHS/United States
GR  - P30 EY019007/EY/NEI NIH HHS/United States
GR  - R01 EY018868/EY/NEI NIH HHS/United States
GR  - R01 EY031210/EY/NEI NIH HHS/United States
PT  - Journal Article
DEP - 20210630
PL  - United States
TA  - Sci Adv
JT  - Science advances
JID - 101653440
SB  - IM
PMC - PMC8245041
EDAT- 2021/07/02 06:00
MHDA- 2021/07/02 06:01
PMCR- 2021/06/30
CRDT- 2021/07/01 06:12
PHST- 2020/10/04 00:00 [received]
PHST- 2021/05/17 00:00 [accepted]
PHST- 2021/07/01 06:12 [entrez]
PHST- 2021/07/02 06:00 [pubmed]
PHST- 2021/07/02 06:01 [medline]
PHST- 2021/06/30 00:00 [pmc-release]
AID - 7/27/eabf1068 [pii]
AID - abf1068 [pii]
AID - 10.1126/sciadv.abf1068 [doi]
PST - epublish
SO  - Sci Adv. 2021 Jun 30;7(27):eabf1068. doi: 10.1126/sciadv.abf1068. Print 2021 Jun.