TY - JOUR
T1 - FGF-induced Pea3 transcription factors program the genetic landscape for cell fate determination
AU - Garg, Ankur
AU - Hannan, Abdul
AU - Wang, Qian
AU - Collins, Tamica
AU - Teng, Siying
AU - Bansal, Mukesh
AU - Zhong, Jian
AU - Xu, Keli
AU - Zhang, Xin
N1 - Publisher Copyright:
© 2018 Garg et al. http://creativecommons.org/licenses/by/4.0/.
PY - 2018/9
Y1 - 2018/9
N2 - FGF signaling is a potent inducer of lacrimal gland development in the eye, capable of transforming the corneal epithelium into glandular tissues. Here, we show that genetic ablation of the Pea3 family of transcription factors not only disrupted the ductal elongation and branching of the lacrimal gland, but also biased the lacrimal gland epithelium toward an epidermal cell fate. Analysis of high-throughput gene expression and chromatin immunoprecipitation data revealed that the Pea3 genes directly control both the positive and negative feedback loops of FGF signaling. Importantly, Pea3 genes are also required to suppress aberrant Notch signaling which, if gone unchecked, can compromise lacrimal gland development by preventing the expression of both Sox and Six family genes. These results demonstrate that Pea3 genes are key FGF early response transcriptional factors, programing the genetic landscape for cell fate determination.
AB - FGF signaling is a potent inducer of lacrimal gland development in the eye, capable of transforming the corneal epithelium into glandular tissues. Here, we show that genetic ablation of the Pea3 family of transcription factors not only disrupted the ductal elongation and branching of the lacrimal gland, but also biased the lacrimal gland epithelium toward an epidermal cell fate. Analysis of high-throughput gene expression and chromatin immunoprecipitation data revealed that the Pea3 genes directly control both the positive and negative feedback loops of FGF signaling. Importantly, Pea3 genes are also required to suppress aberrant Notch signaling which, if gone unchecked, can compromise lacrimal gland development by preventing the expression of both Sox and Six family genes. These results demonstrate that Pea3 genes are key FGF early response transcriptional factors, programing the genetic landscape for cell fate determination.
UR - http://www.scopus.com/inward/record.url?scp=85054074592&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.1007660
DO - 10.1371/journal.pgen.1007660
M3 - Article
C2 - 30188892
AN - SCOPUS:85054074592
SN - 1553-7390
VL - 14
JO - PLoS genetics
JF - PLoS genetics
IS - 9
M1 - e1007660
ER -