Essay About Lung Cell Biology And Use Of Many Different Animal

Essay Preview: Prof
Report this essay
Workshop Summary
Am. J. Respir. Cell Mol. Biol. Vol. 25, pp. 137-140, 2001
Internet address: www.atsjournals.org
Basic Mechanisms of Lung Development
Eighth Woods Hole Conference on Lung Cell Biology 2000
Wellington V. Cardoso and Mary C. Williams
Pulmonary Center, Department of Medicine, Boston University, Boston, Massachusetts
Studies of the molecular regulation of lung development
have reached the log-growth phase. The key questions related
to lung development are formidable ones to answer,
demanding sophisticated and sensitive molecular tools and
the use of many different animal, organ, and cellular experimental
models. The eighth Y2K Woods Hole Conference
on Lung Cell Biology, organized by faculty of the Pulmonary
Center, Boston University School of Medicine, and
supported by the Division of Lung Diseases of the National
Heart, Lung, and Blood Institute, explored some of the recent
research in this basic area of lung cell and molecular biology.
Many of the fundamental questions, concepts, and
observations about basic developmental processes and lung
development have been addressed in recent reviews (1-10).
Fundamental Questions
The fundamental questions in lung development are interesting
but difficult to answer in specific molecular terms. Many,
if not all, of these questions apply to the development of
other organs and are not unique to lung development per se
or to the mammalian lung. For that reason a number of presentations
summarized the current molecular understanding
of model systems including chick limb, tracheal system of
Drosophila
, and organogenesis of the mammalian liver.
Other presentations described postnatal development because
it is well known that certain changes in lung structure
and function, such as alveolization, occur mainly after birth.
The key questions discussed at the meeting included
these: What directs an area of the foregut to become lung,
and what cellular and molecular mechanisms account for
initiation of budding to form the lung? What are the positive
and negative regulators of branching that result in
bronchial tree formation? What signaling pathways are involved,
and what target genes are activated or repressed to
initiate cell proliferation, differentiation, deposition of matrix,
and vasculogenesis of the lung? What are the regulatory
events that result in the proximal-to-distal patterns of
epithelial differentiation? What genes control airway and
alveolar dimensions? How is expression of important lung
genes specifically regulated? What are the developmental
and adult functions of proteins expressed solely and/or
mainly in the lung? How plastic is the phenotype of differentiated
lung cells, both in developing and adult lung?
It is clear that we have assembled lists of molecules that
appear to influence lung development, and other lists describing
changes in cellular, molecular, and organ phenotypes
due to manipulation of the amount, site, or timing of
expression of these molecules. However, we do not understand
well–if at all–the integrated regulatory pathways
that direct the complex processes that produce this highly
patterned, multicellular organ.
Initiation of Lung Bud Formation
What are the events, signaling pathways, and regulatory molecules
that initiate lung bud formation from the foregut in the
first place? The answer is not certain, although interfering with
expression of several molecules can prevent initiation. Studying
the formation of liver and pancreas, also foregut derivatives,
provides some insight into foregut specification. Direct
contact between cardiac mesoderm and foregut epithelium is
required for liver induction. Fibroblast growth factors (FGFs)
from the mesoderm, including FGF-1, -2, and -8, interact with
the endodermal FGF receptors, resulting in the binding to
their cognate
-elements of factors that transactivate liver
genes, such as albumin,
-fetoprotein, and transthyretin.
The transcription factor pancreatic-duodenum homeobox
(PDX)-1 appears to distinguish between sites of liver and
pancreas induction. PDX-1 expression is inhibited by cardiac
mesoderm,