FOXN4

Last update 08 May 2025

Basic Info

Synonyms

forkhead box N4, Forkhead box protein N4, FOXN4

Introduction

Transcription factor essential for neural and some non-neural tissues development, such as retina and lung respectively. Binds to an 11-bp consensus sequence containing the invariant tetranucleotide 5'-ACGC-3'. During development of the central nervous system, is required to specify the amacrine and horizontal cell fates from multipotent retinal progenitors while suppressing the alternative photoreceptor cell fates through activating DLL4-NOTCH signaling. Also acts synergistically with ASCL1/MASH1 to activate DLL4-NOTCH signaling and drive commitment of p2 progenitors to the V2b interneuron fates during spinal cord neurogenesis. In development of non-neural tissues, plays an essential role in the specification of the atrioventricular canal and is indirectly required for patterning the distal airway during lung development (By similarity).

100 Clinical Results associated with FOXN4

100 Translational Medicine associated with FOXN4

0 Patents (Medical) associated with FOXN4

Literatures (Medical) associated with FOXN4

01 Dec 2023·European Journal of Immunology

Foxn1 is not essential for T‐cell development in teleosts

Article

Author: Hess, Isabell ; Boehm, Thomas ; Pietsch, Theodore W ; Schorpp, Michael ; Swann, Jeremy B ; Ho, Hsuan-Ching

AbstractIn mammals, T‐cell development depends on the activity of the Foxn1 transcription factor in the thymic epithelium; mutations in the vertebrate‐specific Foxn1 gene are associated with profound T‐cell lymphopenia and fatal immunodeficiency. Here, we examined the extent of T‐cell development in teleosts lacking a functional foxn1 gene. In zebrafish carrying a deleterious internal deletion of foxn1, reduced but robust lymphopoietic activity is maintained in the mutant thymus. Moreover, pseudogenization or loss of foxn1 in the genomes of deep‐sea anglerfishes is independent of the presence or absence of the canonical signatures of the T‐cell lineage. Thus, in contrast to the situation in mammals, the teleost thymus can support foxn1‐independent lymphopoiesis, most likely through the activity of the Foxn4, an ancient metazoan paralog of Foxn1. Our results imply that during the early stages of vertebrate evolution, genetic control of thymopoiesis was functionally redundant and thus robust; in mammals, the genetic network was reorganized to become uniquely dependent on the FOXN1 transcription factor.

14 Jul 2023·eLife

Forkhead transcription factor FKH-8 cooperates with RFX in the direct regulation of sensory cilia in Caenorhabditis elegans.

Article

Author: Vilar, Marçal ; Tena, Juan J ; Swoboda, Peter ; Esteve-Serrano, Ainara ; Brocal-Ruiz, Rebeca ; Mora-Martínez, Carlos ; Flames, Nuria ; Franco-Rivadeneira, Maria Luisa

Cilia, either motile or non-motile (a.k.a primary or sensory), are complex evolutionarily conserved eukaryotic structures composed of hundreds of proteins required for their assembly, structure and function that are collectively known as the ciliome. Ciliome gene mutations underlie a group of pleiotropic genetic diseases known as ciliopathies. Proper cilium function requires the tight coregulation of ciliome gene transcription, which is only fragmentarily understood. RFX transcription factors (TF) have an evolutionarily conserved role in the direct activation of ciliome genes both in motile and non-motile cilia cell-types. In vertebrates, FoxJ1 and FoxN4 Forkhead (FKH) TFs work with RFX in the direct activation of ciliome genes, exclusively in motile cilia cell-types. No additional TFs have been described to act together with RFX in primary cilia cell-types in any organism. Here we describe FKH-8, a FKH TF, as a direct regulator of the sensory ciliome genes in Caenorhabditis elegans. FKH-8 is expressed in all ciliated neurons in C. elegans, binds the regulatory regions of ciliome genes, regulates ciliome gene expression, cilium morphology and a wide range of behaviors mediated by sensory ciliated neurons. FKH-8 and DAF-19 (C. elegans RFX) physically interact and synergistically regulate ciliome gene expression. C. elegans FKH-8 function can be replaced by mouse FOXJ1 and FOXN4 but not by other members of other mouse FKH subfamilies. In conclusion, RFX and FKH TF families act jointly as direct regulators of ciliome genes also in sensory ciliated cell types suggesting that this regulatory logic could be an ancient trait predating functional cilia sub-specialization.

30 Jun 2023·Cellular and molecular biology (Noisy-le-Grand, France)

FOXN4 affects myocardial ischemia-reperfusion injury through HIF-1α/MMP2-mediated ferroptosis of cardiomyocytes.

Article

Author: Zhang, Guimin ; Yang, Peng ; Yang, Jiaona ; Li, Yan ; Zhou, Xiaojuan ; Deng, Min ; Wang, Jiyang

Myocardial ischemia-reperfusion injury (MIRI) is an important factor leading to myocardial injury and necrosis, and can induce ischemic heart disease. Forkhead box protein N4 (FOXN4) belongs to the gene family of Fork head domain (Fox) transcription factors and plays an important role in heart formation and function. However, whether FOXN4 is involved in MIRI progression is unknown. In this study, we investigated the clinicopathological significance and potential mechanisms of FOXN4 in MIRI. The expressions of FOXN4 and MMP2 were measured by quantitative reverse transcriptase polymerase chain reaction, apoptosis was detected by flow cytometry, and cell viability was detected by examining EdU incorporation into DNA. The signaling pathway related proteins FOXN4, MMP2, HIF-1α, apoptosis-related proteins Bcl-2 and Bax, and ferroptosis-related proteins TFR1 and IREB2 were detected by western blot, the levels of malondialdehyde (MDA), Fe2+, reactive oxygen species (ROS), and glutathione were detected by commercially available kits, and the cardiac histopathology after MIRI was evaluated by hematoxylin and eosin staining. We found that knockdown of FOXN4 alleviated oxidative stress, inhibited ROS production, and inhibited ferroptosis in MIR-injured tissues and cardiomyocytes. In addition, knockdown of FOXN4 inhibited myocardial injury, improved myocardial cell viability, restored myocardial function, and alleviated MIRI. We interrogated the mechanism and found that FOXN4 can enhance its binding to HIF-1α, up-regulate the expression of MMP2, and mediate ferroptosis to regulate the functional activity of cardiomyocytes to affect the progression of MIRI. This study provides new insights into the role of FOXN4 in MIRI progression and suggests that FOXN4 may represent a potential therapeutic target in MIRI progression by regulating the active function of cardiomyocytes through HIF-1α/MMP2-mediated ferroptosis.

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FOXN4

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