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FGF-induced Pea3 transcription factors program the genetic landscape for cell fate determination.

TitleFGF-induced Pea3 transcription factors program the genetic landscape for cell fate determination.
Publication TypeJournal Article
Year of Publication2018
AuthorsGarg A, Hannan A, Wang Q, Collins T, Teng S, Bansal M, Zhong J, Xu K, Zhang X
JournalPLoS Genet
Volume14
Issue9
Paginatione1007660
Date Published2018 Sep 06
ISSN1553-7404
Abstract

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.

DOI10.1371/journal.pgen.1007660
Alternate JournalPLoS Genet.
PubMed ID30188892