Background: Antenatal corticosteroids and surfactant replacement therapy have dramatically reduced mortality caused by lung disease in premature babies. Knowledge about mechanisms regulating epithelial differentiation of the respiratory membrane is limited, as are effects of pharmacological interventions. The chicken fetus is a valuable model for exploring pharmacological actions on developing organs. However, more precise information about the timing of developmental events in the chicken lung is needed for human correlation. Objectives: Characterization of morphological development and protein expression in the respiratory membrane of the developing chicken lung to create a platform for pharmacological testing in a human context. Methods: Fetal chicken lungs, embryonic days (E) 7-20, were characterized by morphology and protein expression of epithelial differentiation markers. This was compared with publications on the same processes during human lung development. Results: The respiratory membranes of developing chicken and human lungs show basic similarities. In chicken, surfactant protein B is expressed in cuboidal type II epithelial cells from E17. Aquaporin 5 is expressed in the epithelium from E7 and selectively in type I pneumocytes from E17. The type I pneumocyte and endothelial marker, caveolin 1, is expressed in the endothelium from E7 to E20. Conclusion: Despite phylogenetic distance, central aspects of cellular development in the chicken and human lung are similar. The fetal chicken model has important additional advantages to mammalian models, including fetal independence and short incubation, and is thus well suited for in vivo studies of lung maturation relevant to human development.

Jobe AH: Lung maturation: the survival miracle of very low birth weight infants. Pediatr Neonatol 2010;51:7-13.
Sullivan LC, Orgeig S: Dexamethasone and epinephrine stimulate surfactant secretion in type II cells of embryonic chickens. Am J Physiol Regul Integr Comp Physiol 2001;281:R770-R777.
Stern CD: The chick; a great model system becomes even greater. Dev Cell 2005;8:9-17.
Moonen RM, Agren P, Cogolludo AL, Perez VF, Villamor E: Response of chicken ductus arteriosus to hypercarbic and normocarbic acidosis. Neonatology 2010;98:47-56.
Been JV, Zoer B, Kloosterboer N, Kessels CG, Zimmermann LJ, van Iwaarden JF, Villamor E: Pulmonary vascular endothelial growth factor expression and disaturated phospholipid content in a chicken model of hypoxia-induced fetal growth restriction. Neonatology 2009;97:183-189.
Maina JN: A systematic study of the development of the airway (bronchial) system of the avian lung from days 3 to 26 of embryogenesis: a transmission electron microscopic study on the domestic fowl, Gallus gallus variant domesticus. Tissue Cell 2003;35:375-391.
Maina JN, West JB, Orgeig S, Foot NJ, Daniels CB, Kiama SG, Gehr P, Muhlfeld C, Blank F, Muller L, Lehmann A, Brandenberger C, Rothen-Rutishauser B: Recent advances into understanding some aspects of the structure and function of mammalian and avian lungs. Physiol Biochem Zool 2010;83:792-807.
Wigglesworth JS: Lung development in the second trimester. Br Med Bull 1988;44:894-908.
Genest DR, Williams MA, Greene MF: Estimating the time of death in stillborn fetuses. I. Histologic evaluation of fetal organs; an autopsy study of 150 stillborns. Obstet Gynecol 1992;80:575-584.
Hamburger V, Hamilton HL: A series of normal stages in the development of the chick embryo. J Morphol 1951;88:49-92.
Kaarteenaho R, Lappi-Blanco E, Lehtonen S: Epithelial N-cadherin and nuclear beta-catenin are up-regulated during early development of human lung. BMC Dev Biol 2010;10:113.
Hamvas A, Deterding RR, Wert SE, White FV, Dishop MK, Alfano DN, Halbower AC, Planer B, Stephan MJ, Uchida DA, Williames LD, Rosenfeld JA, Lebel RR, Young LR, Cole FS, Nogee LM: Heterogeneous pulmonary phenotypes associated with mutations in the thyroid transcription factor gene NKX2-1. Chest 2013;144:794-804.
Zeng X, Yutzey KE, Whitsett JA: Thyroid transcription factor-1, hepatocyte nuclear factor-3beta and surfactant protein A and B in the developing chick lung. J Anat 1998;193:399-408.
Bernhard W, Gebert A, Vieten G, Rau GA, Hohlfeld JM, Postle AD, Freihorst J: Pulmonary surfactant in birds: coping with surface tension in a tubular lung. Am J Physiol Regul Integr Comp Physiol 2001;281:R327-R337.
Bernhard W, Haslam PL, Floros J: From birds to humans: new concepts on airways relative to alveolar surfactant. Am J Respir Cell Mol Biol 2004;30:6-11.
Hughes AL: Evolution of the lung surfactant proteins in birds and mammals. Immunogenetics 2007;59:565-572.
Stahlman MT, Gray ME, Whitsett JA: The ontogeny and distribution of surfactant protein B in human fetuses and newborns. J Histochem Cytochem 1992;40:1471-1480.
Ringman UA, von SK, Zelenina M, Aperia A, Frenckner B: Low pulmonary expression of epithelial Na+ channel and Na+, K+-ATPase in newborn infants with congenital diaphragmatic hernia. Neonatology 2011;99:14-22.
Kreda SM, Gynn MC, Fenstermacher DA, Boucher RC, Gabriel SE: Expression and localization of epithelial aquaporins in the adult human lung. Am J Respir Cell Mol Biol 2001;24:224-234.
Woo J, Lee J, Chae YK, Kim MS, Baek JH, Park JC, Park MJ, Smith IM, Trink B, Ratovitski E, Lee T, Park B, Jang SJ, Soria JC, Califano JA, Sidransky D, Moon C: Overexpression of AQP5, a putative oncogene, promotes cell growth and transformation. Cancer Lett 2008;264:54-62.
Ramirez-Lorca R, Munoz-Cabello AM, Toledo-Aral JJ, Ilundain AA, Echevarria M: Aquaporins in chicken: localization of ck-AQP5 along the small and large intestine. Comp Biochem Physiol A Mol Integr Physiol 2006;143:269-277.
Williams MC: Alveolar type I cells: molecular phenotype and development. Annu Rev Physiol 2003;65:669-695.
Hollins AJ, Campbell L, Gumbleton M, Evans DJ: Caveolin expression during chondrogenesis in the avian limb. Dev Dyn 2002;225:205-211.
Brownfoot FC, Crowther CA, Middleton P: Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2008;4:CD006764.
Reese S, Dalamani G, Kaspers B: The avian lung-associated immune system: a review. Vet Res 2006;37:311-324.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.