Dynamic modulation of Cyp21a1 (21-hydroxylase) expression sites in the mouse developing lung

- The site of Cyp21a1 expression within the lung is changing during development.
- The distal epithelium is the major site of expression up to postnatal day 5.
- Cyp21a1 is expressed in the developing saccules and septa.
- Cyp21a1 expression switches from PTI to capillaries during alveolarization.

21-hydroxylase is expressed in the developing lung where it is proposed as a local source of glucocorticoids playing important roles in lung development. We have studied the precise sites of Cyp21a1 expression in the developing mouse lung from the pseudoglandular stage (gestation day (GD) 15.5) to the alveolar stage (postnatal day (PND) 15) by in situ hybridization. Cyp21a1-mRNA was found mainly in epithelial cells from GD 15.5 to PND 5, but the precise site of expression shifted from the distal epithelium during the pseudoglandular and the canalicular stages including the distal epithelium without lumina, to the proximal epithelium and the wall of developing saccules during the perinatal period (GD 19.5 and PND 0), and to the wall of developing saccules and septa, most probably in type I pneumonocytes (PTI), on PND 5. Cyp21a1 expression changed from PTI cells to capillary endothelial cells of the same distal structures during alveolarization. The mesenchyme was generally negative. Endothelial cells forming large vessels were negative. However the tunica adventitia surrounding arteries was Cyp21a1-positive, while several veins were surrounded by a Cyp21a1-positive layer. In conclusion, Cyp21a1 remains expressed in the most distal structure of the developing lung even though these structures are changing, but its expression is not restricted to these areas. Taken together, our data show the highly dynamic modulation of Cyp21a1 expression sites, consistent with the evolving structures of the developing lung.