The Rar genes are differentially expressed during lung development. Rarb is expressed at high levels in the foregut endoderm prior to lung budding (see Figure 2B,E) [Ruberte et al., 1991; Smith, 1994], and is most likely present in the early lung bud endoderm. During lung branching morphogenesis, it remains expressed along the endoderm of the trachea and the proximal (large) bronchi, but is absent in the distal bronchi and the developing alveolar epithelia (Figure 6B) [Dolle et al., 1990]. Rarg is also expressed, albeit in a more homogeneous manner, in developing lung tissues (Figure 6C). There is ample evidence that RA regulates lung development [Desai et al., 2006; Mendelsohn et al., 1994b], and the RA-dependent molecular interactions are beginning to be unravelled [Chen et al., 2007; Wang et al., 2006]. It appears that RA signaling is required for initial budding and early lung branching, but needs to be downregulated for more distal branching and distal airway formation to proceed to completion [Malpel et al., 2000; Wongtrakool et al., 2003]. In rat, there is persistent expression of RARs in the fetal
