Hoxb-5 expression in the developing mouse lung suggests a role in branching morphogenesis and epithelial cell fate

Abstract

Hoxb-5 is one of the few homeobox genes strongly expressed in the developing mouse lung. To explore the hypothesis that Hoxb-5 acts to regulate epithelial cell fate and branching morphogenesis in the developing lung, we studied the temporal, spatial, and cell-specific expression of Hoxb-5 from gestational day (d) 13.5 to postnatal day (P) 2. Immunocytochemistry demonstrated regional localization of Hoxb-5 protein to developing conducting airways and surrounding mesenchyme. The cellular expression pattern changed from diffusely positive nuclei of mesenchymal cells on d13.5 to become more localized to nuclei of subepithelial fibroblasts and some adjacent columnar and cuboidal epithelial cells on d14.5. After d14.5, Hoxb-5 protein expression continued to decrease in mesenchymal cells distal from developing airways, but persisted in fibroblasts underlying conducting airways. Hoxb-5 protein expression persisted in nuclei of columnar and cuboidal epithelial cells on d16.5 and d17.5, with expression in low cuboidal epithelial cells as well from d17.5 to P2. Western blot analysis showed temporal and quantitative changes in Hoxb-5 protein expression with peak expression on d14.5-15.5. We conclude that Hoxb-5 protein is developmentally regulated in a temporal, spatial, and cell-specific manner throughout the pseudoglandular, canalicular, and terminal saccular periods of lung development in the mouse. This localization and expression pattern suggests that Hoxb-5 may influence branching morphogenesis, cell-cell communication, cell fate, and differentiation of conducting airway epithelia.

The transcriptome of nitrofen-induced pulmonary hypoplasia in the rat model of congenital diaphragmatic hernia

“…MiR-10a is an RA target (36) and is localized in the vicinity of the HOXB cluster of chromosome 17 in humans. The HOXB locus is involved in lung branching morphogenesis and has a putative role in determining cell fate decision in the lung (37). Our study identified nitrofen-mediated upregulation of rno-miR-10b.…”

Extracellular matrix signaling: integration of form and function in normal and malignant cells

“…Although the precise role of SPI-3 has not been established, it could inhibit proteolytic activity and thus support neuronal survival [38]. Interestingly, Hoxb5 has also been linked to branching morphogenesis and epithelial cell fate in developing lung [39], a process which can be profoundly altered by imbalances between ECM-degrading proteinases and their inhibitors [40]. Together these studies reinforce a link between Hox genes and ECM-mediated organogenesis and differentiation.…”

Oxygen differentially affects the hox proteins Hoxb5 and Hoxa5 altering airway branching and lung vascular formation

“…Control lungs grew at a consistent rate from 48 through 96 h of culture (Bogue et al 1994;Aubin et al 1997;Volpe et al 1997Volpe et al , 2000Volpe et al , 2003, we evaluated Hoxb5 and Hoxa5 protein levels and immunolocalization in lungs from the RA and O 2 groups. After 48 h of 0.4 FiO 2 , Hoxb5 protein levels decreased to 50% of control lungs ( Fig.…”