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

Dev Biol. 2017 Sep 1;429(1):44-55. doi: 10.1016/j.ydbio.2017.07.011. Epub 2017 Jul 23.

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.

Keywords: Alveolar type II cells; Cell differentiation; Irx1; Lung; Stem cells; Tooth.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alveolar Epithelial Cells / cytology*
  • Alveolar Epithelial Cells / metabolism
  • Animals
  • Animals, Newborn
  • Cell Differentiation*
  • Crosses, Genetic
  • Dental Enamel / cytology*
  • Embryo, Mammalian / metabolism
  • Embryonic Development / genetics
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism*
  • Female
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Developmental
  • Genotype
  • HEK293 Cells
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Incisor / embryology
  • Incisor / metabolism
  • Lymphoid Enhancer-Binding Factor 1 / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pulmonary Surfactant-Associated Proteins / metabolism
  • Rats
  • SOX9 Transcription Factor / metabolism
  • SOXB1 Transcription Factors / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • FOXJ1 protein, mouse
  • Forkhead Transcription Factors
  • Homeodomain Proteins
  • Irx1 protein, mouse
  • Lymphoid Enhancer-Binding Factor 1
  • Pulmonary Surfactant-Associated Proteins
  • SOX9 Transcription Factor
  • SOXB1 Transcription Factors
  • Transcription Factors