Canonical BMP pathway activation in developing airway epithelial cells Although strong BRE activity was detected in the trachea and primary bronchi as early as E10-E12.5 [33] , consistent with the demonstrated role of BMP signaling in trachea development [48, 49] , BMP-driven eGFP-expression was not detected in the epithelial compartments of the interlobular airways before the canalicular stage of lung development. As shown in Figures 1 and  4A , minimal eGFP expression was detected around E14.5 in the large airways, and only after E17 strong eGFP signal was detected in cartilaginous and large airways following a proximal-distal axis pattern, with more intense signal in the proximal part of the bronchial tree. Immunostaining of BRE-eGFP lung tissue sections with an antibody specific for the Clara cell specific differentiation marker Scgb1a1/CCSP/CC10 (hereafter referred to as CC10), revealed expression of the eGFP reporter from E17.5 and onwards, in luminal cells of the developing airways. Strong CC10 expression was detected around E19.5, approximately two days after the onset of eGFP expression in the airway epithelium ( Figure 4A ) CC10 and eGFP exhibited partially overlapping zones of expression, with eGFP being highly expressed in the proximal portion and CC10 highly expressed in the distal portion of the developing airway tree. A zone of eGFP pos -CC10 pos cells appeared to separate the CC10 pos epithelial population from the eGFP pos airway regions. Postnatal expansion of CC10 pos regions in the conducting airways was accompanied by a gradual reduction of the eGFP pos regions ( Figure 4A ).