Although the development and growth of the mammalian lung is one of the most studied and well documented of all the organs of the body little is known of the actual mechanisms which control and affect its early development. We have started developing model mechanisms for generating the initial branching that takes place in the early development of the lung to try to obtain some understanding of the underlying developmental processes involved. We have constructed a preliminary mathematical model which may describe the formation and development of the lung during the pseudoglandular stages of development. This preliminary model takes into account available experimental evidence and may provide a possible mechanism which describes the dichotomous branching of the lung bud in the early stages. The main features of the model are mechanical factors, such as strain and pressure, which are known to have a major effect on lung cells and their proliferation rates. It is known from experimental results and from our preliminary numerical results that pressure in an inflating axisymmetric thin sheet (which we hypothesize for the limb membrane) gives rise to strain fields and curvature distributions which are maximal at certain regions of the membrane. We are currently investigating whether such fields arising in lung buds may provide the stimulus for mitosis leading to bifurcation in the regions where branching occurs. This work will be written up for publication.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001243-19
Application #
6308545
Study Section
Project Start
1999-12-01
Project End
2000-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
19
Fiscal Year
2000
Total Cost
$23,494
Indirect Cost
Name
University of Washington
Department
Type
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Bassingthwaighte, James B; Butterworth, Erik; Jardine, Bartholomew et al. (2012) Compartmental modeling in the analysis of biological systems. Methods Mol Biol 929:391-438
Dash, Ranjan K; Bassingthwaighte, James B (2010) Erratum to: Blood HbO2 and HbCO2 dissociation curves at varied O2, CO2, pH, 2,3-DPG and temperature levels. Ann Biomed Eng 38:1683-701
Bassingthwaighte, James B; Raymond, Gary M; Butterworth, Erik et al. (2010) Multiscale modeling of metabolism, flows, and exchanges in heterogeneous organs. Ann N Y Acad Sci 1188:111-20
Dash, Ranjan K; Bassingthwaighte, James B (2006) Simultaneous blood-tissue exchange of oxygen, carbon dioxide, bicarbonate, and hydrogen ion. Ann Biomed Eng 34:1129-48
Dash, Ranjan K; Bassingthwaighte, James B (2004) Blood HbO2 and HbCO2 dissociation curves at varied O2, CO2, pH, 2,3-DPG and temperature levels. Ann Biomed Eng 32:1676-93
Kellen, Michael R; Bassingthwaighte, James B (2003) Transient transcapillary exchange of water driven by osmotic forces in the heart. Am J Physiol Heart Circ Physiol 285:H1317-31
Kellen, Michael R; Bassingthwaighte, James B (2003) An integrative model of coupled water and solute exchange in the heart. Am J Physiol Heart Circ Physiol 285:H1303-16
Wang, C Y; Bassingthwaighte, J B (2001) Capillary supply regions. Math Biosci 173:103-14
Swanson, K R; True, L D; Lin, D W et al. (2001) A quantitative model for the dynamics of serum prostate-specific antigen as a marker for cancerous growth: an explanation for a medical anomaly. Am J Pathol 158:2195-9
Swanson, K R; Alvord Jr, E C; Murray, J D (2000) A quantitative model for differential motility of gliomas in grey and white matter. Cell Prolif 33:317-29

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