Advances in Lung Development

Alison A. Hislop, PhD
Institute for Child Health, UCL
30 Guilford St
London WC1N 1EH
United Kingdom
#44 (0)207 905 2337
#44 (0)207 813 8459
The description of the developing lung is well known. The primary goal is to produce a large gas
exchange area within a relatively small volume of thorax. It appears in the 4th week of gestation and by
a process of branching morphogenesis the entire bronchial tree is present by the 16th week of
gestation. Alveoli are first formed in the last 10 weeks of gestation and they continue to form for at
least 2-3 years after birth. Blood vessels appear alongside the airways and alveoli as they form by
vasculogenesis and angiogenesis. Many influences in utero and childhood will lead to a restriction of
normal growth and it is accepted that reduced lung function at birth and in early childhood tracks into
adulthood. Studies on the control of normal and abnormal growth should give us clues as to how we
may repair abnormal lungs and it is this field that is showing the most advances at the moment.
Throughout lung development there is interaction of many growth factors and transcriptional factors. In
addition to these genetic influences there are the physical effects of space, fluid, nutrition and
environment which includes oxygen tensions and maternal smoking. Since airway development is
complete early in gestation it is unlikely that any abnormalities in airway numbers can be reversed.
However alveolar development continues postnatally and it is the encouragement of new alveolar
growth which is studies most using experimental models. Post pneumonectomy or lobectomy there is
increase in lung volume of the residual lung to fill space. This can be a very rapid response. In adult
dogs HIF-1 and vascular endothelial growth factor are increased after only 3 days. Both of these are
known to promote angiogenesis and alveolar formation. Maternal food restriction and deficiency of
Vitamin A and D lead to abnormal lungs in man and other species. In experimental animals
supplemental feedings can restore alveolar growth again very rapidly. Repair in the airways is largely
due to the basal cells of the epithelium while in the alveolar region it is the Type II alveolar cells.
However there are also bronchioalveolar stem cells and a pluripotent side population of cells derived
from the bone marrow. Circulating endothelial progenitor cells can also promote capillary formation.
The combination of these can lead in animals to formation a new alveoli.
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