Biomedical Engineering Reference
In-Depth Information
(Bray, 2006; Ehebauer et al., 2006; Le Borgne, 2006; Jaekel and Klein, 2006;
Moberg et al., 2005; Thompson et al., 2005; Vaccari and Bilder, 2005).
There is increasing evidence on the specific roles of the individual compo-
nents of this pathway in both organogenesis and tissue maintenance throughout
the tracheobronchopulmonary tree (Bettenhausen et al., 1995; Juopperi et al.,
2007; Post et al., 2000). Interestingly, newer studies are involving Notch in the
maintenance of lung CSCs; NSCLC cell lines were found to express Notch-1
and Notch-3 as well as their downstream effector Hes-1. Interestingly, these
proteins were not found in small cell lung cancer (SCLC) cell lines (Chen et al.,
1997; Collins et al., 2004; Dang et al., 2000). Neuroendocrine differentiation in
SCLC depends, in part, on the action of the basic-helix-loop-helix (bHLH)
transcription factor human achaete-scute homologue-1 (hASH1). In contrast to
Notch-1 and Notch-3, hASH1 expression, which is normally inhibited through
Notch, is elevated in neuroendocrine SCLC but seldom in NSCLC (Ball et al.,
1993). These studies suggest that Notch (essential in Clara cell and neuroendo-
crine cell development) is aberrantly regulated in NSCLC and SCLC hinting
toward further potential roles in stem cell fate.
2.4 The Importance of Communication Between Developmental
Pathways
We have highlighted some of the crucial developmental cell signaling pathways
and some of the evidence demonstrating their involvement in normal lung
organogenesis with the aim to then explore how they play a role in tissue
homeostasis and how this is exerted through their action on stem and progeni-
tor pulmonary cells within specific niches or microenvironments. Before we do
that, we must emphasize the importance of crosstalk among these pathways and
the complex relationships between their components. These often occur in
synchronous enhancing or opposing manners, ultimately orchestrating the
function of rare pluripotent cells in the bronchopulmonary tree maintaining
adequate lung function. Understanding these mechanisms of interaction and
their real functional significance is as important as understanding the individual
pathways on their own.
Wnt and Hh signalings are fundamental for the development of diverse
epithelial tissues such as the teeth, the gastrointestinal tract, and hair follicles
(Logan and Nusse, 2004; Hooper and Scott, 2005; Gregorieff and Clevers,
2005). Ectopic activation of these pathways can lead to malignancy (Tables 1
and 2), and inhibition of their function is the culprit of many developmental
abnormalities (Taipale and Beachy, 2001; McMahon et al., 2003). Some proof
regarding the relationship between Wnt and Hh has been reported during
embryonic organogenesis and both pathways have shown protagonism in
epithelial-mesenchymal interactions; the precise mechanisms dictating these
mutual synergistic actions continue to be fairly mysterious (Noramly et al.,
