Genomes and Genes
Gene Symbol: Sftpd
Description: surfactant associated protein D
Alias: AI573415, SP-D, Sfpd, Sftp4, pulmonary surfactant-associated protein D, PSP-D, lung surfactant protein D
- Wert S, Yoshida M, Levine A, Ikegami M, Jones T, Ross G, et al. Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice. Proc Natl Acad Sci U S A. 2000;97:5972-7 pubmed..SP-D plays a critical role in the suppression of alveolar macrophage activation, which may contribute to the pathogenesis of chronic inflammation and emphysema. ..
- Casey J, Kaplan J, Atochina Vasserman E, Gow A, Kadire H, Tomer Y, et al. Alveolar surfactant protein D content modulates bleomycin-induced lung injury. Am J Respir Crit Care Med. 2005;172:869-77 pubmed..These data provide new in vivo evidence for an antiinflammatory role for SP-D in response to noninfectious, subacute lung injury via modulation of oxidative-nitrative stress. ..
- Zhang L, Ikegami M, Crouch E, Korfhagen T, Whitsett J. Activity of pulmonary surfactant protein-D (SP-D) in vivo is dependent on oligomeric structure. J Biol Chem. 2001;276:19214-9 pubmed..Disulfide cross-linked SP-D oligomers are required for the regulation of surfactant phospholipid homeostasis and the prevention of emphysema and foamy macrophages in vivo. ..
- Ikegami M, Na C, Korfhagen T, Whitsett J. Surfactant protein D influences surfactant ultrastructure and uptake by alveolar type II cells. Am J Physiol Lung Cell Mol Physiol. 2005;288:L552-61 pubmed..SP-D regulates uptake and catabolism by type II cells and influences the ultrastructure of surfactant in the alveolus. ..
- Yoshida M, Korfhagen T, Whitsett J. Surfactant protein D regulates NF-kappa B and matrix metalloproteinase production in alveolar macrophages via oxidant-sensitive pathways. J Immunol. 2001;166:7514-9 pubmed..Oxidant production and reactive oxygen species were increased in lungs of SP-D(-/-) mice, in turn activating NF-kappaB and MMP expression. SP-D plays an unexpected inhibitory role in the regulation of NF-kappaB in AMs. ..
- Ochs M, Knudsen L, Allen L, Stumbaugh A, Levitt S, Nyengaard J, et al. GM-CSF mediates alveolar epithelial type II cell changes, but not emphysema-like pathology, in SP-D-deficient mice. Am J Physiol Lung Cell Mol Physiol. 2004;287:L1333-41 pubmed
- Levine A, Whitsett J, Hartshorn K, Crouch E, Korfhagen T. Surfactant protein D enhances clearance of influenza A virus from the lung in vivo. J Immunol. 2001;167:5868-73 pubmed..Since the airway is the usual portal of entry for influenza A virus and other respiratory pathogens, SP-D is likely to play an important role in innate defense responses to IAV. ..
- Zhang L, Hartshorn K, Crouch E, Ikegami M, Whitsett J. Complementation of pulmonary abnormalities in SP-D(-/-) mice with an SP-D/conglutinin fusion protein. J Biol Chem. 2002;277:22453-9 pubmed..Our findings also strongly suggest that the molecular mechanisms underlying impaired pulmonary host defense and abnormal lipid metabolism are distinct from those that promote ongoing inflammation and the development of emphysema. ..
- Compernolle V, Brusselmans K, Acker T, Hoet P, Tjwa M, Beck H, et al. Loss of HIF-2alpha and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nat Med. 2002;8:702-10 pubmed..The pneumotrophic effect of VEGF may have therapeutic potential for lung maturation in preterm infants. ..
- Fisher J, Larson J, Cool C, Dow S. Lymphocyte activation in the lungs of SP-D null mice. Am J Respir Cell Mol Biol. 2002;27:24-33 pubmed..This study therefore provides further evidence of the important local immunoregulatory role of SP-D in vivo. ..
- Atochina E, Gow A, Beck J, Haczku A, Inch A, Kadire H, et al. Delayed clearance of pneumocystis carinii infection, increased inflammation, and altered nitric oxide metabolism in lungs of surfactant protein-D knockout mice. J Infect Dis. 2004;189:1528-39 pubmed..These results indicate that SP-D plays a role in host defense against P. carinii in vivo by modulating clearance of organisms, lung inflammation, and metabolism of NO...
- Guo C, Atochina Vasserman E, Abramova E, Foley J, Zaman A, Crouch E, et al. S-nitrosylation of surfactant protein-D controls inflammatory function. PLoS Biol. 2008;6:e266 pubmed publisher..This represents new insight into both the regulation of protein function by S-nitrosylation and NO's role in innate immunity. ..
- Lemos M, McKinney J, Rhee K. Dispensability of surfactant proteins A and D in immune control of Mycobacterium tuberculosis infection following aerosol challenge of mice. Infect Immun. 2011;79:1077-85 pubmed publisher..tuberculosis were unaltered in all genotypes tested. Together, these data indicate that SP-A and SP-D are dispensable for immune control of M. tuberculosis in a low-dose, aerosol challenge, murine model of tuberculosis (TB). ..
- Mun J, Tam C, Kowbel D, Hawgood S, Barnett M, Evans D, et al. Clearance of Pseudomonas aeruginosa from a healthy ocular surface involves surfactant protein D and is compromised by bacterial elastase in a murine null-infection model. Infect Immun. 2009;77:2392-8 pubmed publisher..aeruginosa from the healthy ocular surface and that proteases can compromise that clearance. The data also suggest that SP-D degradation in vivo is a mechanism by which P. aeruginosa proteases could contribute to virulence...
- Qi L, Kash J, Dugan V, Jagger B, Lau Y, Sheng Z, et al. The ability of pandemic influenza virus hemagglutinins to induce lower respiratory pathology is associated with decreased surfactant protein D binding. Virology. 2011;412:426-34 pubmed publisher..We also explored whether there was an association between the ability of lung surfactant protein D (SP-D) to bind to the HA and the ability of the corresponding chimeric virus to infect bronchiolar and ..
- Wong C, Akiyama J, Allen L, Hawgood S. Localization and developmental expression of surfactant proteins D and A in the respiratory tract of the mouse. Pediatr Res. 1996;39:930-7 pubmed..In addition, these studies provide the first documentation that, unlike SP-A, SP-D is synthesized not only in the lung but also in submucosal glands of the trachea. ..
- Douda D, Jackson R, Grasemann H, Palaniyar N. Innate immune collectin surfactant protein D simultaneously binds both neutrophil extracellular traps and carbohydrate ligands and promotes bacterial trapping. J Immunol. 2011;187:1856-65 pubmed publisher..Collectively, these findings provide a unique biological relevance for SP-D-DNA interactions and places SP-D as an important innate immune protein that promotes bacterial trapping by NETs during neutrophil-mediated host defense. ..
- Bird A, Flecknoe S, Tan K, Olsson P, Antony N, Mantamadiotis T, et al. cAMP response element binding protein is required for differentiation of respiratory epithelium during murine development. PLoS ONE. 2011;6:e17843 pubmed publisher..Together, these results demonstrate a crucial role for Creb1 activity for the development and differentiation of the conducting and distal lung epithelium. ..
- Collins R, Ikegami M, Korfhagen T, Whitsett J, Sly P. In vivo measurements of changes in respiratory mechanics with age in mice deficient in surfactant protein D. Pediatr Res. 2003;53:463-7 pubmed..These data demonstrate that the changes in lung structure in SP-D (-/-) mice are reflected in the mechanical properties of both airway and lung parenchyma measured in vivo. ..
- Vandivier R, Ogden C, Fadok V, Hoffmann P, Brown K, Botto M, et al. Role of surfactant proteins A, D, and C1q in the clearance of apoptotic cells in vivo and in vitro: calreticulin and CD91 as a common collectin receptor complex. J Immunol. 2002;169:3978-86 pubmed
- Ikegami M, Hull W, Yoshida M, Wert S, Whitsett J. SP-D and GM-CSF regulate surfactant homeostasis via distinct mechanisms. Am J Physiol Lung Cell Mol Physiol. 2001;281:L697-703 pubmed..Taken together, these findings demonstrate the distinct roles of SP-D and GM-CSF in the regulation of surfactant homeostasis and lung structure...
- O Brien K, Alberich Jorda M, Yadav N, Kocher O, Diruscio A, Ebralidze A, et al. CARM1 is required for proper control of proliferation and differentiation of pulmonary epithelial cells. Development. 2010;137:2147-56 pubmed publisher..These results demonstrate for the first time that CARM1 inhibits pulmonary cell proliferation and is required for proper differentiation of alveolar cells. ..
- Fujita M, Shannon J, Ouchi H, Voelker D, Nakanishi Y, Mason R. Serum surfactant protein D is increased in acute and chronic inflammation in mice. Cytokine. 2005;31:25-33 pubmed..These data clarified profile of SP-A and SP-D in acute and chronic inflammation and indicated that serum SP-D can serve as a biomarker of lung inflammation in both acute and chronic lung injury in mice. ..
- Kishore U, Greenhough T, Waters P, Shrive A, Ghai R, Kamran M, et al. Surfactant proteins SP-A and SP-D: structure, function and receptors. Mol Immunol. 2006;43:1293-315 pubmed..We also try to put in perspective the controversial subject of the candidate receptor molecules for SP-A and SP-D. ..
- Gaunsbaek M, Rasmussen K, Beers M, Atochina Vasserman E, Hansen S. Lung surfactant protein D (SP-D) response and regulation during acute and chronic lung injury. Lung. 2013;191:295-303 pubmed publisher..The study also confirms the concept of using increased SP-D serum levels as a biomarker of especially chronic airway inflammation. ..
- Hansen S, Schmidt V, Steffensen M, Jensen P, Gjerstorff M, Thiel S, et al. An enzyme-linked immunosorbent assay (ELISA) for quantification of mouse surfactant protein D (SP-D). J Immunol Methods. 2008;330:75-85 pubmed..8 ng/ml). With this ELISA, it will be possible to study the regulation of SP-D in various mouse models and upon various stimuli. ..
- Desai T, Brownfield D, Krasnow M. Alveolar progenitor and stem cells in lung development, renewal and cancer. Nature. 2014;507:190-4 pubmed publisher..We propose that local signals regulate AT2 stem-cell activity: a signal transduced by EGFR-KRAS controls self-renewal and is hijacked during oncogenesis, whereas another signal controls reprogramming to AT1 fate. ..
- McCormick C, Hobden J, Balzli C, Reed J, Caballero A, Denard B, et al. Surfactant protein D in Pseudomonas aeruginosa keratitis. Ocul Immunol Inflamm. 2007;15:371-9 pubmed..0233). Surfactant D is important to the ocular innate host defense against Pseudomonas keratitis. ..
- Ikegami M, Whitsett J, Jobe A, Ross G, Fisher J, Korfhagen T. Surfactant metabolism in SP-D gene-targeted mice. Am J Physiol Lung Cell Mol Physiol. 2000;279:L468-76 pubmed..SP-D deficiency results in multiple abnormalities in surfactant forms and metabolism that cannot be attributed to a single mechanism...
- Crouch E, Smith K, McDonald B, Briner D, Linders B, McDonald J, et al. Species differences in the carbohydrate binding preferences of surfactant protein D. Am J Respir Cell Mol Biol. 2006;35:84-94 pubmed..Thus, ligand recognition by human SP-D involves a complex interplay between saccharide presentation, the valency of trimeric subunits, and species-specific residues that flank the primary carbohydrate binding site. ..
- Motwani M, White R, Guo N, Dowler L, Tauber A, Sastry K. Mouse surfactant protein-D. cDNA cloning, characterization, and gene localization to chromosome 14. J Immunol. 1995;155:5671-7 pubmed..The mouse SP-D gene (Sftp4) has been localized to chromosome 14 (to a region syntenic to human chromosome 10), closely linked to the genes ..
- Botas C, Poulain F, Akiyama J, Brown C, Allen L, Goerke J, et al. Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D. Proc Natl Acad Sci U S A. 1998;95:11869-74 pubmed..The findings in the SP-D-deficient mice suggest a role for SP-D in surfactant homeostasis. ..
- LeVine A, Elliott J, Whitsett J, Srikiatkhachorn A, Crouch E, DeSilva N, et al. Surfactant protein-d enhances phagocytosis and pulmonary clearance of respiratory syncytial virus. Am J Respir Cell Mol Biol. 2004;31:193-9 pubmed..Because the airway is the usual portal of entry for RSV and other respiratory pathogens, the local production of SP-D is likely to play a role in innate defense responses to inhaled viruses. ..
- Tecle T, White M, Sorensen G, Gantz D, Kacak N, Holmskov U, et al. Critical role for cross-linking of trimeric lectin domains of surfactant protein D in antiviral activity against influenza A virus. Biochem J. 2008;412:323-9 pubmed publisher..These results show that antiviral activities of SP-D can be reproduced without the N-terminal and collagen domains and that cross-linking of NCRDs is essential for antiviral activity of SP-D with respect to IAV. ..
- Giannoni E, Sawa T, Allen L, Wiener Kronish J, Hawgood S. Surfactant proteins A and D enhance pulmonary clearance of Pseudomonas aeruginosa. Am J Respir Cell Mol Biol. 2006;34:704-10 pubmed..aeruginosa by stimulating phagocytosis by alveolar macrophages and by modulating the inflammatory response in the lungs. These findings also show that the functions of SP-A and SP-D are not completely redundant in vivo. ..
- Dave V, Childs T, Whitsett J. Nuclear factor of activated T cells regulates transcription of the surfactant protein D gene (Sftpd) via direct interaction with thyroid transcription factor-1 in lung epithelial cells. J Biol Chem. 2004;279:34578-88 pubmed..Here, we identify a role of nuclear factor of activated T cells (NFATs) in regulation of murine SP-D gene (Sftpd) transcription...
- Atochina Vasserman E, Abramova E, Tomer Y, Scott P, Nazarov V, Kruglov S, et al. SP-D-dependent regulation of NO metabolism in lipopolysaccharide-stimulated peritoneal macrophages. Bull Exp Biol Med. 2009;147:415-20 pubmed..Our results suggest that surfactant protein D is involved in the immune response in the whole organism, but not only in the lungs. The effect of surfactant protein D depends on the phenotype of macrophages. ..
- Korfhagen T, Sheftelyevich V, Burhans M, Bruno M, Ross G, Wert S, et al. Surfactant protein-D regulates surfactant phospholipid homeostasis in vivo. J Biol Chem. 1998;273:28438-43 pubmed..Targeting of the mouse SP-D gene caused accumulation of surfactant lipid and altered phospholipid structures, demonstrating a previously unsuspected role for SP-D in surfactant lipid homeostasis in vivo. ..
- Madan T, Reid K, Singh M, Sarma P, Kishore U. Susceptibility of mice genetically deficient in the surfactant protein (SP)-A or SP-D gene to pulmonary hypersensitivity induced by antigens and allergens of Aspergillus fumigatus. J Immunol. 2005;174:6943-54 pubmed..These data reaffirm an important role for SP-A and SP-D in offering resistance to pulmonary allergenic challenge. ..
- Wan H, Xu Y, Ikegami M, Stahlman M, Kaestner K, Ang S, et al. Foxa2 is required for transition to air breathing at birth. Proc Natl Acad Sci U S A. 2004;101:14449-54 pubmed..Foxa2 regulates a complex pulmonary program of epithelial cell maturation required for transition to air breathing at birth. ..
- Sorensen G, Madsen J, Kejling K, Tornoe I, Nielsen O, Townsend P, et al. Surfactant protein D is proatherogenic in mice. Am J Physiol Heart Circ Physiol. 2006;290:H2286-94 pubmed..The effect is likely to be due to the observed disturbances of plasma lipid metabolism and alteration of the inflammatory process, which underlie the reduced susceptibility to atherosclerosis in Spd-/- mice. ..
- Clark H, Palaniyar N, Strong P, Edmondson J, Hawgood S, Reid K. Surfactant protein D reduces alveolar macrophage apoptosis in vivo. J Immunol. 2002;169:2892-9 pubmed
- George C, Goss K, Meyerholz D, Lamb F, Snyder J. Surfactant-associated protein A provides critical immunoprotection in neonatal mice. Infect Immun. 2008;76:380-90 pubmed
- Zhang J, Liu Z, Zhang T, Lin Z, Li Z, Zhang A, et al. Loss of Lysyl Oxidase-like 3 Attenuates Embryonic Lung Development in Mice. Sci Rep. 2016;6:33856 pubmed publisher..Increased transforming growth factor ?1 (TGF?1) expression might be involved in the up-regulation of LOXL4 in LOXL3-deficient lungs. We concluded that the loss of LOXL3 attenuates mouse embryonic lung development. ..
- Groves A, Gow A, Massa C, Hall L, Laskin J, Laskin D. Age-related increases in ozone-induced injury and altered pulmonary mechanics in mice with progressive lung inflammation. Am J Physiol Lung Cell Mol Physiol. 2013;305:L555-68 pubmed publisher..studies we determined whether progressive pulmonary inflammation associated with aging in surfactant protein D (Sftpd)-/- mice leads to an exacerbated response to ozone...
- Takimoto T, Yoshida M, Hirata H, Kashiwa Y, Takeda Y, Goya S, et al. 4-Hydroxy-2-nonenal induces chronic obstructive pulmonary disease-like histopathologic changes in mice. Biochem Biophys Res Commun. 2012;420:84-90 pubmed publisher..4-HNE induced the accumulation of inflammatory cells expressing high levels of MMP-2 and MMP-9. Our results indicate that 4-HNE production during oxidative stress is a key pathway in the pathogenesis of COPD. ..
- Hawgood S, Akiyama J, Brown C, Allen L, Li G, Poulain F. GM-CSF mediates alveolar macrophage proliferation and type II cell hypertrophy in SP-D gene-targeted mice. Am J Physiol Lung Cell Mol Physiol. 2001;280:L1148-56 pubmed
- Liu Z, Shi Q, Liu J, Abdel Razek O, Xu Y, Cooney R, et al. Innate Immune Molecule Surfactant Protein D Attenuates Sepsis-induced Acute Pancreatic Injury through Modulating Apoptosis and NF-ÎºB-mediated Inflammation. Sci Rep. 2015;5:17798 pubmed publisher..05) from KO mice compared to WT mice. Collectively, these results demonstrate SP-D plays protective roles by inhibiting apoptosis and modulating NF-ÎºB-mediated inflammation in CLP-induced API. ..
- Dias J, Macedo A, Ferreira G, Peterson F, Volkman B, Goodfellow B. The first structure from the SOUL/HBP family of heme-binding proteins, murine P22HBP. J Biol Chem. 2006;281:31553-61 pubmed..In an attempt to assess the structural basis for tetrapyrrole binding in the SOUL/HBP family, models for the p22HBP-protoporphyrin-IX complex and the SOUL protein were generated by manual docking and automated methods. ..
- Jain D, Atochina Vasserman E, Tomer Y, Kadire H, Beers M. Surfactant protein D protects against acute hyperoxic lung injury. Am J Respir Crit Care Med. 2008;178:805-13 pubmed publisher..Local expression of SP-D protects against hyperoxic lung injury through modulation of proinflammatory cytokines and antioxidant enzymatic scavenger systems. ..
- Schwingshackl A, Lopez B, Teng B, Luellen C, Lesage F, Belperio J, et al. Hyperoxia treatment of TREK-1/TREK-2/TRAAK-deficient mice is associated with a reduction in surfactant proteins. Am J Physiol Lung Cell Mol Physiol. 2017;313:L1030-L1046 pubmed publisher..1/thyroid transcription factor-1 (TTF-1) or c-jun, or lamellar body levels. Prophylactic Curosurf administration did not improve lung injury scores or compliance in triple KO mice. ..
- Sun L, Lee D, Zhang Q, Xiao W, Raabe E, Meeker A, et al. Growth retardation and premature aging phenotypes in mice with disruption of the SNF2-like gene, PASG. Genes Dev. 2004;18:1035-46 pubmed..PASG mutant mice provide a useful model for the study of aging as well as the mechanisms regulating epigenetic patterning during development and postnatal life...
- van Eijk M, Haagsman H, Skinner T, Archibald A, Reid K, Lawson P, et al. Porcine lung surfactant protein D: complementary DNA cloning, chromosomal localization, and tissue distribution. J Immunol. 2000;164:1442-50 pubmed..The genes for SP-D and SP-A were also shown to colocalize to a region of porcine chromosome 14 that is syntenic with the human and murine collectin loci. ..
- Kay S, Madan T. Fertility defects in Surfactant associated protein D knockout female mice: altered ovarian hormone profile. Mol Immunol. 2016;71:87-97 pubmed publisherSurfactant associated protein D (SFTPD, also known as SP-D), a pattern recognition molecule, is an integral component of the mucosal immune system of female reproductive tract (FRT)...
- Antony N, McDougall A, Mantamadiotis T, Cole T, Bird A. Creb1 regulates late stage mammalian lung development via respiratory epithelial and mesenchymal-independent mechanisms. Sci Rep. 2016;6:25569 pubmed publisher..Together our results suggest that the requirement of Creb1 for normal mammalian lung morphogenesis is not dependent upon its expression in lung epithelium or mesenchyme, nor its role in musculoskeletal development. ..
- Fakih D, Pilecki B, Schlosser A, Jepsen C, Thomsen L, OrmhÃ¸j M, et al. Protective effects of surfactant protein D treatment in 1,3-Î²-glucan-modulated allergic inflammation. Am J Physiol Lung Cell Mol Physiol. 2015;309:L1333-43 pubmed publisherSurfactant protein D (SP-D) is a pulmonary collectin important in lung immunity. SP-D-deficient mice (Sftpd(-/-)) are reported to be susceptible to ovalbumin (OVA)- and fungal allergen-induced pulmonary inflammation, while treatment with ..
- Zhang Z, Abdel Razek O, Hawgood S, Wang G. Protective Role of Surfactant Protein D in Ocular Staphylococcus aureus Infection. PLoS ONE. 2015;10:e0138597 pubmed publisher..aureus infection but cysteine protease impairs SP-D function in this murine model, and that cysteine protease inhibitor may be a potential therapeutic agent in S. aureus keratitis. ..
- Huang Y, Kapere Ochieng J, Kempen M, Munck A, Swagemakers S, van Ijcken W, et al. Hypoxia inducible factor 3? plays a critical role in alveolarization and distal epithelial cell differentiation during mouse lung development. PLoS ONE. 2013;8:e57695 pubmed publisher..Moreover, Hif3? affected the expression of genes not typically involved in the hypoxia response, providing evidence for a novel function of Hif3? beyond the hypoxia response. ..
- Yu H, Wessels A, Chen J, Phelps A, Oatis J, Tint G, et al. Late gestational lung hypoplasia in a mouse model of the Smith-Lemli-Opitz syndrome. BMC Dev Biol. 2004;4:1 pubmed..The molecular mechanism of impaired lung development associated with sterol deficiency by Dhcr7 loss is still unknown, but these results do not support the involvement of dysregulated Shh-Patched-Gli pathway in causing this defect. ..
- King B, Kingma P. Surfactant protein D deficiency increases lung injury during endotoxemia. Am J Respir Cell Mol Biol. 2011;44:709-15 pubmed publisher..by intraperitoneal injection of LPS and direct lung injury by intratracheal injection of LPS in wild-type and Sftpd(-/-) mice to elucidate the role of SP-D during ALI/ARDS...
- Xu B, Qu X, Gu S, Doughman Y, Watanabe M, Dunwoodie S, et al. Cited2 is required for fetal lung maturation. Dev Biol. 2008;317:95-105 pubmed publisher..We propose that the Cited2-Tcfap2c complex controls lung maturation by regulating Cebpa expression. Understanding the function of this complex may provide novel therapeutic strategies for patients with respiratory distress syndromes. ..
- Tenner A. Membrane receptors for soluble defense collagens. Curr Opin Immunol. 1999;11:34-41 pubmed
- Kishimoto K, Nishizuka M, Ueda T, Kajita K, Ugawa S, Shimada S, et al. Indispensable role of factor for adipocyte differentiation 104 (fad104) in lung maturation. Exp Cell Res. 2011;317:2110-23 pubmed publisher..Collectively, these results indicate that fad104 has an indispensable role in lung maturation, especially the maturation and differentiation of ATII cells. ..
- Liu W, Purevdorj E, Zscheppang K, von Mayersbach D, Behrens J, Brinkhaus M, et al. ErbB4 regulates the timely progression of late fetal lung development. Biochim Biophys Acta. 2010;1803:832-9 pubmed publisher..We conclude that pulmonary ErbB4 deletion results in a structural and functional delay in fetal lung development, indicating a crucial regulatory role of ErbB4 in the timely progression of fetal lung development. ..