2 4113.4 Specification of Lung Progenitors
The endoderm of the primitive foregut develops organ-specific domains represent-
ing the primordial thyroid, lung, esophagus, stomach, liver, and pancreas between
E8.0 and E9.5 in mouse development (Cardoso and Kotton 2008 ; Serls et al. 2005 ).
Gradients of WNT2/2B, FGF, and BMP signals from the surrounding mesoderm are
established by expression of these factors as well as the BMP antagonist, Noggin,
and result in patterning of the anterior foregut along its dorsal/ventral (D/V) axis.
During this time period, Sox2 is expressed dorsally in the future esophagus but
downregulated ventrally, where it suppresses Nkx2–1. Nkx2–1 expression, mean-
while, is induced ventrally in the site of the future trachea (Morrisey and Hogan
2010 ) (Fig. 13.2). While it remains the earliest known marker of primordial lung
progenitor cells, Nkx2–1 is not essential to specify the respiratory lineage, as Nkx2–
1 −/− mice develop lung tissue despite defects in other aspects of lung development
Fig. 13.2 Anterior foregut patterning – this schematic illustrates a section of the developing fore-
gut at approximately E8.5–E9.0 of mouse embryonic differentiation, prior to lung budding and
separation of the foregut into the lung and esophagus. Gradients of BMP and Wnt signaling are
generated along the dorsal/ventral axis promoting the expression of Sox2 dorsally in the region of
the future esophagus and the induction of Nkx2–1+ lung progenitors ventrally in the region that
will become the lung
13 Development and Bioengineering of Lung Regeneration