HOXA5 plays tissue-specific roles in the developing respiratory system

Development. 2017 Oct 1;144(19):3547-3561. doi: 10.1242/dev.152686. Epub 2017 Aug 21.

Abstract

Hoxa5 is essential for development of several organs and tissues. In the respiratory system, loss of Hoxa5 function causes neonatal death due to respiratory distress. Expression of HOXA5 protein in mesenchyme of the respiratory tract and in phrenic motor neurons of the central nervous system led us to address the individual contribution of these Hoxa5 expression domains using a conditional gene targeting approach. Hoxa5 does not play a cell-autonomous role in lung epithelium, consistent with lack of HOXA5 expression in this cell layer. In contrast, ablation of Hoxa5 in mesenchyme perturbed trachea development, lung epithelial cell differentiation and lung growth. Further, deletion of Hoxa5 in motor neurons resulted in abnormal diaphragm innervation and musculature, and lung hypoplasia. It also reproduced the neonatal lethality observed in null mutants, indicating that the defective diaphragm is the main cause of impaired survival at birth. Thus, Hoxa5 possesses tissue-specific functions that differentially contribute to the morphogenesis of the respiratory tract.

Keywords: Diaphragm; Hoxa5; Lung; Mouse; Respiratory system development; Trachea.

MeSH terms

  • Animals
  • Animals, Newborn
  • Body Patterning / genetics
  • Cartilage / embryology
  • Cartilage / metabolism
  • Cell Differentiation / genetics
  • Crosses, Genetic
  • Diaphragm / innervation
  • Diaphragm / metabolism
  • Diaphragm / ultrastructure
  • Female
  • Gene Deletion
  • Gene Expression Regulation, Developmental
  • Genotype
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Male
  • Mesoderm / embryology
  • Mesoderm / metabolism
  • Models, Biological
  • Motor Neurons / metabolism
  • Muscle Development
  • Muscle Fibers, Skeletal / metabolism
  • Organ Specificity / genetics
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Respiratory Mucosa / metabolism
  • Respiratory System / embryology*
  • Respiratory System / metabolism*
  • SOX9 Transcription Factor / metabolism
  • Signal Transduction / genetics
  • Survival Analysis
  • Trachea / embryology
  • Trachea / metabolism
  • Transcription Factors

Substances

  • Homeodomain Proteins
  • Hoxa5 protein, mouse
  • Phosphoproteins
  • SOX9 Transcription Factor
  • Transcription Factors