FOXN1: A Master Regulator Gene of Thymic Epithelial Development Program

Romano, Rosa; Palamaro, Loredana; Fusco, Anna; Giardino, Giuliana; Gallo, Vera; Vecchio, Luigi Del; Pignata, Claudio

doi:10.3389/fimmu.2013.00187

Cited by 73 publications

(65 citation statements)

References 155 publications

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“…In all vertebrates studied so far, FoxN1 plays an essential role in thymus development (Ma et al, 2012;Neves et al, 2012;Lee et al, 2013;Romano et al, 2013). Moreover, in mammals, FoxN1 is essential for hair formation whereas it is also expressed in chick during feather development (Darnell et al, 2014).…”

Section: Foxn1/4a and Foxn2/3 Expressionmentioning

confidence: 99%

Expression of Fox genes in the cephalochordate Branchiostoma lanceolatum

et al. 2015

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Forkhead box (Fox) genes code for transcription factors that play important roles in different biological processes. They are found in a wide variety of organisms and appeared in unicellular eukaryotes. In metazoans, the gene family includes many members that can be subdivided into 24 classes. Cephalochordates are key organisms to understand the functional evolution of gene families in the chordate lineage due to their phylogenetic position as an early divergent chordate, their simple anatomy and genome structure. In the genome of the cephalochordate amphioxus Branchiostoma floridae, 32 Fox genes were identified, with at least one member for each of the classes that were present in the ancestor of bilaterians. In this work we describe the expression pattern of 13 of these genes during the embryonic development of the Mediterranean amphioxus, Branchiostoma lanceolatum. We found that FoxK and FoxM genes present an ubiquitous expression while all the others show specific expression patterns restricted to diverse embryonic territories. Many of these expression patterns are conserved with vertebrates, suggesting that the main functions of Fox genes in chordates were present in their common ancestor.

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Section: Foxn1/4a and Foxn2/3 Expressionmentioning

confidence: 99%

Expression of Fox genes in the cephalochordate Branchiostoma lanceolatum

et al. 2015

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“…More than 20 years ago, it was shown by positional cloning that a loss-of-function mutation in the Foxn1 gene, originally named winged-helix nude (Whn) or HNF3/forkhead homolog-11 (Hfh11), is responsible for the loss of a functional DBD (28). The role of FOXN1 in the formation of the thymus and immunological system is studied extensively and has recently been reviewed in detail (23,29,30). Briefly, thymic epithelial cell lineages express the FOXN1 transcription factor, which is essential for T cell development (31,32).…”

Section: Nude Phenotypementioning

confidence: 99%

FOXN1 Transcription Factor in Epithelial Growth and Wound Healing

Grabowska

Wilanowski

2017

Molecular and Cellular Biology

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FOXN1 is a prodifferentiation transcription factor in the skin epithelium. Recently, it has also emerged as an important player in controlling the skin wound healing process, as it actively participates in reepithelialization and is thought to be responsible for scar formation. FOXN1 positivity is also a feature of pigmented keratinocytes, including nevi, and FOXN1 is an attribute of benign epithelial tumors. The lack of FOXN1 favors the skin regeneration process displayed by nude mice, pointing to FOXN1 as a switch between regeneration and reparative processes. The stem cell niche provides a functional source of cells after the loss of tissue following wounding. The involvement of prodifferentiation factors in the regulation of this pool of stem cells is suggested. However, the exact mechanism is still under question, and we speculate that the FOXN1 transcription factor is involved in this process. This review analyzes the pleiotropic effects of FOXN1 in the skin, its function in the tumorigenesis process, and its potential role in depletion of the stem cell niche after injury, as well as its suggested mechanistic role, acting in a cell-autonomous and a non-cell-autonomous manner during skin self-renewal.

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“…A mutation within the FOXN1 gene of the nude mice results in inhibition of the mouse immune system and also a lack of body hair giving it its nude appearance. The disrupted FOXN1 gene causes athymia resulting in an absence of mature T cells (Romano et al 2013). This impaired immune system therefore fails to reject xenografts making it possible to study HNSCC in solid tumors.…”

Section: In Vivo -Xenograft Modelmentioning

confidence: 99%

Understanding the Role of EGFR in the Treatment of Head and Neck Squamous Cell Carcinoma

Jedliński¹

2014

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Head and neck squamous cell carcinoma (HNSCC) originates from the epithelial lining of the upper aerodigestive tract. It accounts for over 90 % of the malignancies found in the head and neck region. 600,000 new cases of HNSCC occur each year worldwide. Apart from causing painful lesions, HNSCC directly impacts the patient’s fundamental functions such as breathing and eating and also can disrupt the patient’s senses such as smell, taste, speech and even vision. Most cases of HNSCC require a combination of different treatments such as surgery, chemotherapy (primarily cisplatin based), and radiotherapy. Treatment decisions are largely based on the size of the tumor, the involvement of local lymph nodes, and distant spread. Treatment resistance and local recurrence are significant problems and to date no form of clinical treatment sensitivity prediction is available. A majority of HNSCC tumors overexpresses the epidermal growth factor receptor (EGFR). This receptor is involved in proliferation and DNA repair and is the target of a monoclonal antibody named cetuximab that selectively binds and inhibits EGFR. It is the only targeted therapy available to HNSCC patients and reserved for late stage patients in Sweden. Numerous investigators have searched for predictive markers and we hypothesized that since HNSCC is a very heterogeneous disease a single factor would not be able to predict the treatment outcome. In paper I we explore a panel of predictive factors using a point system, called the number of negative points (NNP), in which we could combine both proteins and genetic variations in an attempt to find a set of markers that could predict the intrinsic cisplatin sensitivity (ICS). The expression level of EGFR, Hsp70, Bax, Bcl-XL, survivin, and COX-2 was determined in 39 HNSCC cell lines. Moreover, the p53, MDM2, FGFR4, XPC, XPD, XRCC1, and XRCC3 genes were analyzed for the presence of specific single nucleotide polymorphisms (SNPs). Pearson’s correlation tests showed that EGFR was the only protein that alone correlated to ICS (r=0.388, P=0.015). The strongest correlation to ICS was found when combining SNPs in XRCC3 and XPD with the expression of EGFR, Hsp70, Bax, and Bcl-2 using the NNP system (r=0.614 P≤0.001). In paper II we assess the intrinsic radiosensitivity (IR), the ICS, and the intrinsic cetuximab sensitivity (ICmabS) as well as their combinations in 25 HNSCC cell lines established from HNSCC biopsies taken at the Department of Otorhinolaryngology and Head and Neck Surgery at Linköping University Hospital. Furthermore we investigate the EGFR status (consisting of EGFR gene copy number, EGFR mRNA, EGFR protein, pEGFR), pAkt and mRNA levels of the seven known EGFR ligands. No correlation was found between the different treatment sensitivities. Cetuximab treatment response was significantly correlated to epiregulin (EREG) mRNA expression (r=-0.408, P=0.043). Cetuximab resistant cell lines tended to have low levels of pEGFR (P=0.13) while resistant cell lines had a significantly lower expression of EGFR pro...

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FOXN1: A Master Regulator Gene of Thymic Epithelial Development Program

Cited by 73 publications

References 155 publications

Expression of Fox genes in the cephalochordate Branchiostoma lanceolatum

Expression of Fox genes in the cephalochordate Branchiostoma lanceolatum

FOXN1 Transcription Factor in Epithelial Growth and Wound Healing

Understanding the Role of EGFR in the Treatment of Head and Neck Squamous Cell Carcinoma

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