EMBRYONIC MOUSE LUNG EPITHELIAL PROGENITOR CELLS COEXPRESS IMMUNOHISTOCHEMICAL MARKERS OF DIVERSE MATURE CELL LINEAGES

Developmental expression of marker genes representative of different m ature cell types can be used to study differentiation of cell lineages . We used immunohistochemistry to study expression in developing mouse lung of calcitonin gene related peptide (CGRP), Clara cell 10-KD prot ein (CC10), and surfactant protein-A (SP-A), markers that are differen tially expressed in neuroendocrine cells, Clara cells, and Type II alv eolar cells. Two distinct developmental phases were revealed, The earl ier phase (embryonic days 13-15; E13-E15) was characterized by CGRP, C C10 and SP-A immunostaining in all epithelial cells of the distal airw ays, with the three patterns being virtually identical in adjacent sec tions. The later phase (E16-E18) was characterized by emergence of sta ining of the differentiated cell types. These expression patterns were recapitulated in serumless organ culture, demonstrating that informat ion necessary to generate both phases of gene expression is present wi thin the lung anlage by E11. We conclude that CGRP, CC10, and SP-A are co-expressed in most or all cells of the distal lung epithelium at E1 3-E15 and later become restricted to different cell lineages. This tra nsient expression in progenitor cells of gene products characteristic of diverse differentiated cell types may reflect an underlying mechani sm of gene regulation.