Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 683

Forkhead box factor FoxM1 does not alter lung growth, in particular epithelial
proliferation and airway morphogenesis, but prevents lung maturation and causes
postnatal respiratory failure, as it is required for adaptation to air breathing [ 1400 ].
It is necessary for alveolus epithelial type-1 cell differentiation and synthesis of
mucin-type type-1 integral membrane glycoprotein podoplanin (Pdpn), 6 aquaporin-
5, and surfactant protein-A to -D. Moreover, it is a transcriptional activator of the
genes that encode surfactant protein-A and -B. In adddition, FoxP2 contributes to
postnatal lung alveolarization.

11.3.2.6 Other Transcription Factors

Many other transcription factors are produced in cells of the primitive lung, such as
NKx2-1, GATA5 and GATA6, members of the C/EBP family, HoxA5 and HoxB3
to HoxB5, and nMyC, as well as intracellular (nuclear) receptors such as the
glucocorticoid receptor (GR or NR3c1) [ 1396 ].

11.3.3 Mechanical Basis of Branching

Mechanical forces contribute to tissue morphogenesis, as they can shape epithelial
sheets. Cadherins engaged in homophilic complexes between apposed cells interact
with cortical actin-myosin filaments. Intercellular adhesion sites transmit forces
generated in- and outside involved epi- or endothelial cells. Moreover, cadherin-
based adhesion loci create forces that tend to lengthen these cell contacts, whereas
cortical tensions exerted by actin-myosin filaments tend to shorten them [ 1394 ].
Monolayers of epi(endo)thelial cells that organize to locally minimize its poten-
tial energy and reach a stable equilibrium have been modeled as sheets. Mechanical
modeling will then have to be applied to more complex structures, such as capillaries
covered by a single cell layer and conduits coated by pseudo- and stratified epithelia,
as well as epithelia associated with a mucous layer.

11.3.4 Molecular Basis of Branching

11.3.4.1 Signaling in the Vasculature

In the vasculature, vascular endothelial growth factor, especially VEGFa via
VEGFR2, causes angiogenic sprouting. Tip cells emit numerous filopodia and
migrate in a given direction under the guidance of VEGFa (Chap. 10 ). Whereas tip

6 A.k.a. aggrus, glycoprotein GP36, GP38, and GP40, and T1

α

.