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

Autor: Siying Teng, Tamica N. Collins, Abdul Hannan, Mukesh Bansal, Jian Zhong, Qian Wang, Ankur Garg, Xin Zhang, Keli Xu
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Cancer Research
Fibroblast Growth Factor
Physiology
Organogenesis
Fibroblast growth factor
Biochemistry
Epithelium
Mice
Endocrinology
0302 clinical medicine
Cell Signaling
Gene expression
Medicine and Health Sciences
Small interfering RNAs
SOX Transcription Factors
Genetics (clinical)
Mice
Knockout
Notch Signaling
Regulation of gene expression
Receptors
Notch
Cell determination
Lacrimal Apparatus
Gene Expression Regulation
Developmental
Cell Differentiation
Cell biology
Nucleic acids
medicine.anatomical_structure
Anatomy
Research Article
Signal Transduction
lcsh:QH426-470
DNA transcription
Notch signaling pathway
Lacrimal gland
Cell fate determination
Biology
03 medical and health sciences
Organ Culture Techniques
Growth Factors
DNA-binding proteins
Transcription factors
Genetics
medicine
Animals
Gene Regulation
Non-coding RNA
Molecular Biology
Transcription factor
Ecology
Evolution
Behavior and Systematics
Homeodomain Proteins
Biology and life sciences
Endocrine Physiology
Proteins
Epithelial Cells
Cell Biology
Regulatory Proteins
Gland Development
Fibroblast Growth Factors
body regions
Ophthalmology
lcsh:Genetics
Biological Tissue
030104 developmental biology
Epidermal Cells
RNA
Cytology
Organism Development
Chromatin immunoprecipitation
030217 neurology & neurosurgery
Developmental Biology
Zdroj: PLoS Genetics, Vol 14, Iss 9, p e1007660 (2018)
PLoS Genetics
ISSN: 1553-7404
1553-7390
Popis: 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.
Author summary FGF signaling regulates cell fate decision by inducing genome-wide changes in gene expression. We identified Pea3 family transcription factors as the key effectors of FGF signaling in reprograming the epithelia transcriptome. Pea3 factors control both the feedback and feedforward circuities of FGF signaling in lacrimal gland development. They also activate specific expression of Six and Sox family genes and suppress aberrant activation of Notch signaling. In the absence of Pea3 genes, the lacrimal gland progenitors become epidermal-like in their gene expression patterns. The study of Pea3 function resolves the long standing conundrum of how FGF induces the lacrimal gland fate, providing direction for regenerating the lacrimal gland to treat dry eye diseases.
Databáze: OpenAIRE
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