Irx1 regulates dental outer enamel epithelial and lung alveolar type II epithelial differentiation

Abstract

The Iroquois genes (Irx) appear to regulate fundamental processes that lead to cell proliferation, differentiation, and maturation during development. In this report, the Iroquois homeobox 1 (Irx1) transcription factor was functionally disrupted using a LacZ insert and LacZ expression demonstrated stage-specific expression during embryogenesis. Irx1 is highly expressed in the brain, lung, digits, kidney, testis and developing teeth. Irx1 null mice are neonatal lethal and this lethality it due to pulmonary immaturity. Irx1−/− mice show delayed lung maturation characterized by defective surfactant protein secretion and Irx1 marks a population of SP-C expressing alveolar type II cells. Irx1 is specifically expressed in the outer enamel epithelium (OEE), stellate reticulum (SR) and stratum intermedium (SI) layers of the developing tooth. Irx1 mediates dental epithelial cell differentiation in the lower incisors resulting in delayed growth of the lower incisors. Irx1 is specifically and temporally expressed during developmental stages and we have focused on lung and dental development in this report. Irx1+ cells are unique to the development of the incisor outer enamel epithelium, patterning of Lef-1+ and Sox2+ cells as well as a new marker for lung alveolar type II cells. Mechanistically, Irx1 regulates Foxj1 and Sox9 to control cell differentiation during development.

Single-Cell RNA-Sequencing From Mouse Incisor Reveals Dental Epithelial Cell-Type Specific Genes

“…Few reports had previously indicated the role of OEE in the regulation of tooth germ size. Iroquois homeobox 1 ( Irx1 ) transcription factor was expressed preferentially in OEE, SR, and SI cells ( Supplementary Figure 5 ) and its disruption caused a delay of tooth growth in mouse ( Yu et al, 2017 ). OEE cells are known to contribute to root formation by constituting Hertwig’s epithelial root sheath.…”

Downregulated microRNA‐150 upregulates IRX1 to depress proliferation, migration, and invasion, but boost apoptosis of gastric cancer cells

“…Prior researchers have proved the suppressive role of miR‐544 in iroquois homeobox 1 (IRX1) gene expression in gastric cancer . IRX1 is a member of IRX family, which encodes proteins with a homeobox domain and a characteristic Iroquois domain in the C terminal region . Evidence has shown that diminution of IRX1 expression mediated by protein arginine methyltransferase 5 is capable of contributing to gastric cancer tumorigenicity and metastasis .…”

“…8 IRX1 is a member of IRX family, which encodes proteins with a homeobox domain and a characteristic Iroquois domain in the C terminal region. 9 Evidence has shown that diminution of IRX1 expression mediated by protein arginine methyltransferase 5 is capable of contributing to gastric cancer tumorigenicity and metastasis. 10 IRX1 hypomethylation has been reported to facilitate osteosarcoma metastasis through induction of chemokine (C-X-C motif) ligand 14 (CXCL14)/nuclear factor κB (NF-κB) signaling.…”

DNA Methyltransferases and Gastric Cancer: Insight Into Targeted Therapy

“…It seems that the function of notch pathway components is ambiguous as they were reported either as suppressor or activator of gastric carcinoma, and their exact effect on different steps of gastric cancer pathogenesis still remains unclear [40,42,[44][45]. Iroquois homeobox 1 (IRX1) is a member of Iroquois homeobox factors family that is required for embryonic development [46]. Down-regulation of IRX1 has been reported in several cancers including gastric cancer.…”