Biomedical Engineering Reference
In-Depth Information
created. Cells with Clara cell markers can give birth to ciliated cells. In the proximal
airways, columnar epithelial cells give rise to basal cells. Basal cells can self-renew
and contribute to other cell lineages. On the other hand, differentiated ciliated cells
do not divide [
1393
].
Patterning information specifies branching time and loci during development as
well as the length, shape and direction of outgrowth of each branch. Branching
does not occur randomly to fill available space. This process is precisely controlled.
Nevertheless, coding is simplified by repeated use of a branching mechanism, using
an algorithm such as that in Mandelbrot's fractal model [
1392
].
11.3.2
Airway Morphogenesis Mediators
Several morphological processes with feedbacks control branching initiation and
extension that rely on activation, competition, and interaction for tip and stalk as-
signment in growing branches, migration, proliferation, and survival of involved cell
types [
1394
]. Moreover, cells implicated in lumenogenesis undergo an apicobasal
polarization with an apical side building the lumen (Sect.
10.2.5
).
Before birth, peripheral saccules are created and pulmonary capillaries grow in
close apposition to the alveolar epithelium for gas exchange. Pulmonary immaturity
and lack of pulmonary surfactant cause respiratory distress syndrome. Surfactant
function relies especially on surfactant protein-B and -C, and ABCa3 transporter.
Budding and growth of the respiratory tree involve numerous growth fac-
tors, signaling proteins, and matrix components, as well as transcription factors
(Sect.
11.3.4.2
).
11.3.2.1
Growth Factors
In mice, lung formation begins at 9.5 days postcoitum (E9.5), when the foregut
endoderm invades the splanchnic mesenchyme and undergoes dichotomous branch-
ing. Branching morphogenesis depends on mesenchymal-epithelial cell signaling
using fibroblast (FGF10), hepatocyte (HGF), and transforming (TGF
)growth
factors, bone morphogenetic protein BMP4, sonic Hedgehog, and Wnt morphogen
(Sect.
11.3.4.2
). Factors EGF, FGF, and PDGF are involved in alveologenesis.
β
Fibroblast Growth Factors
Fibroblast growth factors are important regulators of the respiratory tract genesis.
Fibroblast growth factor-7 and -10 diffuse from the mesenchyme and activate
alternatively splice variant IIIb (of extracellular loop III) of protein Tyr kinase
receptor FGFR2IIIb in the nearby epithelium and induce budding that is composed
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