Respiratory System Development

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Respiratory system overview (stage 13)

The respiratory system does not carry out its physiological function (of gas exchange) until after birth. The respiratory tract, diaphragm and lungs do form early in embryonic development. The respiratory tract is divided anatomically into 2 main parts:

  1. upper respiratory tract, consisting of the nose, nasal cavity and the pharynx
  2. lower respiratory tract consisting of the larynx, trachea, bronchi and the lungs.

In the head/neck region, the pharynx forms a major arched cavity within the phrayngeal arches. The lungs go through 4 distinct histological phases of development and in late fetal development thyroid hormone, respiratory motions and amniotic fliud are thought to have a role in lung maturation. The two main respiratory cell types, squamous alveolar type 1 and alveolar type 2 (surfactant secreting), both arise from the same bi-potetial progenitor cell.[1] The third main cell type are macrophages (dust cells) that arise from blood monocyte cells.

Development of this system is not completed until the last weeks of Fetal development, just before birth. Therefore premature babies have difficulties associated with insufficient surfactant (end month 6 alveolar cells type 2 appear and begin to secrete surfactant).

Respiratory Links: Introduction | Science Lecture | Med Lecture | Stage 13 | Stage 22 | Upper Respiratory Tract | Diaphragm | Histology | Postnatal | Abnormalities | Respiratory Quiz | Category:Respiratory
Historic Embryology  
1902 The Nasal Cavities and Olfactory Structures | 1906 Lung | 1912 Upper Respiratory Tract | 1912 Respiratory | 1914 Phrenic Nerve | 1918 Respiratory images | 1921 Respiratory | 1922 Chick Pulmonary Vessels | 1934 Right Fetal Lung | 1936 Early Human Lung | 1937 Terminal Air Passages | 1938 Human Histology
Respiratory epithelium cell development.[2]

Some Recent Findings

  • Development and plasticity of alveolar type 1 cells[3] "Alveolar type 1 (AT1) cells cover >95% of the gas exchange surface and are extremely thin to facilitate passive gas diffusion. The development of these highly specialized cells and its coordination with the formation of the honeycomb-like alveolar structure are poorly understood. Using new marker-based stereology and single-cell imaging methods, we show that AT1 cells in the mouse lung form expansive thin cellular extensions via a non-proliferative two-step process while retaining cellular plasticity. In the flattening step, AT1 cells undergo molecular specification and remodel cell junctions while remaining connected to their epithelial neighbors. In the folding step, AT1 cells increase in size by more than 10-fold and undergo cellular morphogenesis that matches capillary and secondary septa formation, resulting in a single AT1 cell spanning multiple alveoli. Furthermore, AT1 cells are an unexpected source of VEGFA and their normal development is required for alveolar angiogenesis. Notably, a majority of AT1 cells proliferate upon ectopic SOX2 expression and undergo stage-dependent cell fate reprogramming."
  • Clonal Dynamics Reveal Two Distinct Populations of Basal Cells in Slow-Turnover Airway Epithelium[2] "We investigated the mouse tracheal epithelial lineage at homeostasis by using long-term clonal analysis and mathematical modeling. This pseudostratified epithelium contains basal cells and secretory and multiciliated luminal cells. Our analysis revealed that basal cells are heterogeneous, comprising approximately equal numbers of multipotent stem cells and committed precursors, which persist in the basal layer for 11 days before differentiating to luminal fate. We confirmed the molecular and functional differences within the basal population by using single-cell qRT-PCR and further lineage labeling. Additionally, we show that self-renewal of short-lived secretory cells is a feature of homeostasis. We have thus revealed early luminal commitment of cells that are morphologically indistinguishable from stem cells."
  • Notch3-Jagged signaling controls the pool of undifferentiated airway progenitors[4] "Basal cells are multipotent airway progenitors that generate distinct epithelial cell phenotypes crucial for homeostasis and repair of the conducting airways. Little is known about how these progenitor cells expand and transition to differentiation to form the pseudostratified airway epithelium in the developing and adult lung. Here, we show by genetic and pharmacological approaches that endogenous activation of Notch3 signaling selectively controls the pool of undifferentiated progenitors of upper airways available for differentiation. This mechanism depends on the availability of Jag1 and Jag2, and is key to generating a population of parabasal cells that later activates Notch1 and Notch2 for secretory-multiciliated cell fate selection." Notch
  • Alveolar progenitor and stem cells in lung development[1] "Alveoli are gas-exchange sacs lined by squamous alveolar type (AT) 1 cells and cuboidal, surfactant-secreting AT2 cells. Classical studies suggested that AT1 arise from AT2 cells, but recent studies propose other sources. Here we use molecular markers, lineage tracing and clonal analysis to map alveolar progenitors throughout the mouse lifespan. We show that, during development, AT1 and AT2 cells arise directly from a bipotent progenitor, whereas after birth new AT1 cells derive from rare, self-renewing, long-lived, mature AT2 cells that produce slowly expanding clonal foci of alveolar renewal."
  • Lung epithelial branching program antagonizes alveolar differentiation[5] "Mammalian organs, including the lung and kidney, often adopt a branched structure to achieve high efficiency and capacity of their physiological functions. Formation of a functional lung requires two developmental processes: branching morphogenesis, which builds a tree-like tubular network, and alveolar differentiation, which generates specialized epithelial cells for gas exchange. ...We thus propose that lung epithelial progenitors continuously balance between branching morphogenesis and alveolar differentiation, and such a balance is mediated by dual-function regulators, including Kras and Sox9. The resulting temporal delay of differentiation by the branching program may provide new insights to lung immaturity in preterm neonates and the increase in organ complexity during evolution."
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches

Search term: Lung Embryology

Aysun Caglar Torun, Serife Tutuncu, Burcu Ustun, Hızır Ufuk Akdemir A Study of the Therapeutic Effects of Resveratrol on Blunt Chest Trauma-Induced Acute Lung Injury in Rats and the Potential Role of Endocan as a Biomarker of Inflammation. Inflammation: 2017; PubMed 28726014

Maria Caracausi, Allison Piovesan, Francesca Antonaros, Pierluigi Strippoli, Lorenza Vitale, Maria Chiara Pelleri Systematic identification of human housekeeping genes possibly useful as references in gene expression studies. Mol Med Rep: 2017; PubMed 28713914

Changcheng Chen, Lili Xu, Yi Xu, Ping Li, Shuo Liu, Bin You Unroofed Coronary Sinus Syndrome: An Easily Corrected Congenital Anomaly But More Diagnostic Suspicions Are Needed. Heart Lung Circ: 2017; PubMed 28709918

Navessa P Tania, Harm Maarsingh, I Sophie T Bos, Andrea Mattiotti, Stuti Prakash, Wim Timens, Quinn D Gunst, Luis J Jimenez-Borreguero, Martina Schmidt, Maurice J B van den Hoff, Reinoud Gosens Endothelial follistatin-like-1 regulates the postnatal development of the pulmonary vasculature by modulating BMP/Smad signaling. Pulm Circ: 2017, 7(1);219-231 PubMed 28680581

Joanna Pancewicz-Wojtkiewicz, Pawel Leszek Bernatowicz The Effect of Afatinib Treatment in Non-small Cell Lung Cancer Cells. Anticancer Res.: 2017, 37(7);3543-3546 PubMed 28668844

Older papers  
  • Suppression of embryonic lung branching morphogenesis[6] "The role of HOM/C homeobox genes on rat embryonic lung branching morphogenesis was investigated using the lung bud explant culture system in an air/liquid interface. ...These results suggest a critical role for homeobox b3 and b4 genes in lung airway branching morphogenesis."
  • Retinoic acid-dependent network in the foregut controls formation of the mouse lung primordium[7] "The developmental abnormalities associated with disruption of signaling by retinoic acid (RA), the biologically active form of vitamin A, have been known for decades from studies in animal models and humans. These include defects in the respiratory system, such as lung hypoplasia and agenesis. ....The data in this study suggest that disruption of Wnt/Tgfbeta/Fgf10 interactions represents the molecular basis for the classically reported failure to form lung buds in vitamin A deficiency."


  • Lung Function and Respiratory Symptoms at 11 Years in Extremely Preterm Children[8] "Following extremely preterm birth, impaired lung function and increased respiratory morbidity persist into middle childhood, especially those with bronchopulmonary dysplasia (BPD). Many of these children may not be receiving appropriate treatment."
  • Pediatric lung transplantation.[9] "Lung transplantation is an accepted therapy for selected pediatric patients with severe end-stage vascular or parenchymal lung disease. Collaboration between the patients' primary care physicians, the lung transplant team, patients, and patients' families is essential. The challenges of this treatment include the limited availability of suitable donor organs, the toxicity of immunosuppressive medications needed to prevent rejection, the prevention and treatment of obliterative bronchiolitis, and maximizing growth, development, and quality of life of the recipients. This article describes the current status of pediatric lung transplantation, indications for listing, evaluation of recipient and donor, updates on the operative procedure,graft dysfunction, and the risk factors, outcomes, and future directions."


  • Moore, K.L., Persaud, T.V.N. & Torchia, M.G. (2015). The developing human: clinically oriented embryology (10th ed.). Philadelphia: Saunders. Chapter 10 Respiratory System
  • Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone. Chapter 11 Development of the Respiratory System and Body Cavities
  • Before We Are Born (5th ed.) Moore and Persaud Chapter 13 p255-287
  • Essentials of Human Embryology Larson Chapter 9 p123-146
  • Human Embryology Fitzgerald and Fitzgerald Chapter 19,20 p119-123
  • Anatomy of the Human Body 1918 Henry Gray The Respiratory Apparatus


  • Describe the development of the respiratory system from the endodermal and mesodermal components.
  • Describe the main steps in the development of the lungs.
  • Describe the development of the diaphragm and thoracic cavities.
  • List the respiratory changes before and after birth.
  • Describe the developmental aberrations responsible for the following malformations: tracheo - oesophageal fistula (T.O.F); oesphageal atresia; diaphragmatic hernia; lobar emphysema.

Development Overview


Week 4 - laryngotracheal groove forms on floor foregut.

Week 5 - left and right lung buds push into the pericardioperitoneal canals (primordia of pleural cavity)

Week 6 - descent of heart and lungs into thorax. Pleuroperitoneal foramen closes.

Week 7 - enlargement of liver stops descent of heart and lungs.

Month 3-6 - lungs appear glandular, end month 6 alveolar cells type 2 appear and begin to secrete surfactant.

Month 7 - respiratory bronchioles proliferate and end in alveolar ducts and sacs.

Lung Development Stages

Lung alveoli development cartoon.jpg

The sequence is most important rather than the actual timing, which is variable in the existing literature.

Human Lung Stages

Stage Human Features
Embryonic week 4 to 5 lung buds originate as an outgrowth from the ventral wall of the foregut where lobar division occurs
Pseudoglandular week 5 to 17 conducting epithelial tubes surrounded by thick mesenchyme are formed, extensive airway branching
Canalicular week 16 to 25 bronchioles are produced, increasing number of capillaries in close contact with cuboidal epithelium and the beginning of alveolar epithelium development
Saccular week 24 to 40 alveolar ducts and air sacs are developed
Alveolar late fetal to 8 years secondary septation occurs, marked increase of the number and size of capillaries and alveoli


Human Embryonic Lung Development
Bailey287.jpg Bailey288.jpg Bailey289.jpg
CRL 4.3 mm, Week 4-5, Stage 12 to 13 CRL 8.5 mm, Week 5, Stage 15 to 16 CRL 10.5 mm, Week 6 Stage 16 to 17
  • Endoderm - tubular ventral growth from foregut pharynx.
  • Mesoderm - mesenchyme of lung buds.
  • Intraembryonic coelom - pleural cavities elongated spaces connecting pericardial and peritoneal spaces.

Pseudoglandular stage

respiratory histology week 8
Respiratory histology (week 8)
  • week 5 - 17
  • tubular branching of the human lung airways continues
  • by 2 months all segmental bronchi are present.
  • lungs have appearance of a glandlike structure.
  • stage is critical for the formation of all conducting airways.
  • lined with tall columnar epithelium, the more distal structures are lined with cuboidal epithelium.
Human right lung 7-8 weeks.jpg

Human lung pseudoglandular stage[10]

Canalicular stage

  • week 16 - 24
  • Lung morphology changes dramatically
  • differentiation of the pulmonary epithelium results in the formation of the future air-blood tissue barrier.
  • Surfactant synthesis and the canalization of the lung parenchyma by capillaries begin.
  • future gas exchange regions can be distinguished from the future conducting airways of the lungs.

Saccular stage

  • week 24 to near term.
  • most peripheral airways form widened airspaces, termed saccules.
  • saccules widen and lengthen the airspace (by the addition of new generations).
  • future gas exchange region expands significantly.
  • Fibroblastic cells also undergo differentiation, they produce extracellular matrix, collagen, and elastin. May have a role in epithelial differentiation and control of surfactant secretion
  • The vascular tree also grows in length and diameter during this time.

Alveolar sac structure

Alveolar stage

  • near term through postnatal period.
  • 1-3 years postnatally alveoli continue to form through a septation process increasing the gas exchange surface area.
  • microvascular maturation occurs during this period.
  • respiratory motions and amniotic fluid are thought to have a role in lung maturation.

Premature babies have difficulties associated with insufficient surfactant (end month 6 alveolar cells type 2 appear and begin to secrete surfactant).

Respiratory secondary septum

Respiratory secondary septum[11]

Respiratory Species Comparison

Mouse lung development[12]
Gestational age (days)
Species Term Embryonic Pseudoglandular Canalicular Saccular
Human 280 < 42 52 - 112 112 - 168 168
Primate 168 < 42 57 - 80 80 - 140 140
Sheep 150 < 40 40 - 80 80 - 120 120
Rabbit 32 < 18 21 - 24 24 - 27 27
Rat 22 < 13 16 - 19 19 - 20 21
Mouse 20 < 9 16 18 19

Table modified from[13]


The following images are from a recent study of the development of bronchial branching in he mouse between E10 to E14.[14]

Mesenchyme (red) and epithelium (blue) the study used knockout mice to show the role of Wnt signalling in branching morphogenesis.

Mouse respiratory 36 to 60 somites.jpg

Mouse respiratory 44 to 60 somites.jpg

Links: Wnt | Mouse Development

Embryonic Respiratory Development

Lung development stage13-22.jpg

Pseudoglandular Respiratory Development

Human lung pseudoglandular.jpg

Pseudoglandular period identified in this paper (GA weeks 12 to 16)

Human lung at pseudoglandular stage showing E- and N-cadherin and β-catenin localization.[15]

Endocrine Lung

Neonatal Human Fetal Rabbit
Neonatal human pulmonary neuroendocrine cell EM01.jpg Fetal rabbit neuroepithelial body 01.jpg
Pulmonary neuroendocrine cell (EM)[16] Neuroepithelial body[16]

Pulmonary neuroendocrine cells (PNECs)

  • develop in late embryonic to early fetal period.[17][18]
  • later in mid-fetal period clusters of these cells form neuroepithelial bodies (NEBs).
  • first cell type to differentiate in the airway epithelium.
    • differentiation regulated by proneural genes - mammalian homolog of the achaete-scute complex (Mash-1) and hairy and enhancer of split1 (Hes-1).[19]
  • located in the fetal lung at bronchiole branching points.
  • may stimulate mitosis to increase branching.
  • secrete 2 peptides - gastrin-releasing peptide (GRP) and calcitonin gene related peptide (CGRP)

Links: Endocrine - Other Tissues | OMIM - GRP | OMIM - CGRP

Lung Histology

Fetal lung histology.jpg
Fetal lung histology

Links: Respiratory System - Histology

Birth Changes

At birth the lung epithelium changes from a prenatal secretory to a postnatal absorptive function. Several factors have been identified as influencing this transport change including: epinephrine, oxygen, glucocorticoids, and thyroid hormones (for review see [20])

Upper Respiratory Tract

Adult upper respiratory tract conducting system
  • part of foregut development
  • anatomically the nose, nasal cavity and the pharynx
  • the pharynx forms a major arched cavity within the pharyngeal arches


The animations below allow a comparison of early and late embryonic lung development. Compare the size and relative position of the respiratory structures and their anatomical relationship to the developing gastrointestinal tract.

Page | Play
Early embryo (stage 13)

3 dimensional reconstruction based upon a serial reconstruction from individual Carnegie stage 13 embryo slice images.

Page | Play
Late embryo (stage 22)

3 dimensional reconstruction based upon a serial reconstruction from individual embryo slice images Carnegie stage 22, 27 mm Human embryo, approximate day 56.

Lung Cardiovascular

Links: Cardiovascular System Development

Pulmonary Circulation

  • pulmonary arteries and veins arise by vasculogenesis[21]

Pulmonary Veins

  • vasculogenesis in the mesenchyme surrounding the terminal buds during the pseudoglandular stage.
    • vasculogenesis - describes the formation of new blood vessels from pluripotent precursor cells.
  • angiogenesis in the canalicular and alveolar stages.
    • angiogenesis - describes the formation of new vessels from pre-existing vessels.

See also review [22]

Bronchial Circulation

Bronchial Arteries

  • vascularising the walls of the airways and the large pulmonary vessels providing giving oxygen and nutrients.
  • extend within the bronchial tree to the periphery of the alveolar ducts.
  • not found in the lungs until around 8 weeks of gestation.
    • one or two small vessels extend from the dorsal aorta and run into the lung alongside the cartilage plates of the main bronchus.

Bronchial Veins

  • small bronchial veins within the airway wall drain into the pulmonary veins.
  • large bronchial veins seen close to the hilum and drain into the cardinal veins and the right atrium.

See review [22]


Mouse respiratory Tbx4 and Tbx5 model[23]
Mouse respiratory development[24]
Fibroblast growth factor signaling[24]
  • Nkx2-1 (Titf1) - ventral wall of the anterior foregut, identifies the future trachea.
  • Localized Fgf10 expression not required for lung branching but prevents epithelial differentiation[25] "As the lung buds grow out, proximal epithelial cells become further and further displaced from the distal source of Fgf10 and differentiate into bronchial epithelial cells. Interestingly, our data presented here show that once epithelial cells are committed to the Sox2-positive airway epithelial cell fate, Fgf10 prevents ciliated cell differentiation and promotes basal cell differentiation."
  • Opposing Fgf and Bmp activities regulate the specification of olfactory sensory and respiratory epithelial cell fates[26] " In this study, we provide evidence that in both chick and mouse, Bmp signals promote respiratory epithelial character, whereas Fgf signals are required for the generation of sensory epithelial cells. Moreover, olfactory placodal cells can switch between sensory and respiratory epithelial cell fates in response to Fgf and Bmp activity, respectively. Our results provide evidence that Fgf activity suppresses and restricts the ability of Bmp signals to induce respiratory cell fate in the nasal epithelium."
  • Heparan sulfate in lung morphogenesis[27] "Heparan sulfate (HS) is a structurally complex polysaccharide located on the cell surface and in the extracellular matrix, where it participates in numerous biological processes through interactions with a vast number of regulatory proteins such as growth factors and morphogens. ...he potential contribution of HS to abnormalities of lung development has yet to be explored to any significant extent, which is somewhat surprising given the abnormal lung phenotype exhibited by mutant mice synthesizing abnormal HS."
  • Signaling via Alk5 controls the ontogeny of lung Clara cells[28] "Clara cells, together with ciliated and pulmonary neuroendocrine cells, make up the epithelium of the bronchioles along the conducting airways. Clara cells are also known as progenitor or stem cells during lung regeneration after injury. ...Using lung epithelial cells, we show that Alk5-regulated Hes1 expression is stimulated through Pten and the MEK/ERK and PI3K/AKT pathways. Thus, the signaling pathway by which TGFbeta/ALK5 regulates Clara cell differentiation may entail inhibition of Pten expression, which in turn activates ERK and AKT phosphorylation."
  • Wt1 and retinoic acid signaling in the subcoelomic mesenchyme control the development of the pleuropericardial membranes and the sinus horns[29] "Pericardium and sinus horn formation are coupled and depend on the expansion and correct temporal release of pleuropericardial membranes from the underlying subcoelomic mesenchyme. Wt1 and downstream Raldh2/retinoic acid signaling are crucial regulators of this process."

Links: Sox | StemBook - Specification and patterning of the respiratory system


  1. 1.0 1.1 Tushar J Desai, Douglas G Brownfield, Mark A Krasnow Alveolar progenitor and stem cells in lung development, renewal and cancer. Nature: 2014, 507(7491);190-4 PubMed 24499815
  2. 2.0 2.1 Julie K Watson, Steffen Rulands, Adam C Wilkinson, Aline Wuidart, Marielle Ousset, Alexandra Van Keymeulen, Berthold Göttgens, Cédric Blanpain, Benjamin D Simons, Emma L Rawlins Clonal Dynamics Reveal Two Distinct Populations of Basal Cells in Slow-Turnover Airway Epithelium. Cell Rep: 2015, 12(1);90-101 PubMed 26119728 | Cell Rep.
  3. Jun Yang, Belinda J Hernandez, Denise Martinez Alanis, Odemaris Narvaez, Lisandra Vila-Ellis, Haruhiko Akiyama, Scott E Evans, Edwin J Ostrin, Jichao Chen Development and plasticity of alveolar type 1 cells. Development: 2015; PubMed 26586225
  4. Munemasa Mori, John E Mahoney, Maria R Stupnikov, Jesus R Paez-Cortez, Aleksander D Szymaniak, Xaralabos Varelas, Dan B Herrick, James Schwob, Hong Zhang, Wellington V Cardoso Notch3-Jagged signaling controls the pool of undifferentiated airway progenitors. Development: 2015, 142(2);258-67 PubMed 25564622
  5. Daniel R Chang, Denise Martinez Alanis, Rachel K Miller, Hong Ji, Haruhiko Akiyama, Pierre D McCrea, Jichao Chen Lung epithelial branching program antagonizes alveolar differentiation. Proc. Natl. Acad. Sci. U.S.A.: 2013, 110(45);18042-51 PubMed 24058167
  6. Tatsuya Yoshimi, Fumiko Hashimoto, Shigeru Takahashi, Yuji Takahashi Suppression of embryonic lung branching morphogenesis by antisense oligonucleotides against HOM/C homeobox factors. In Vitro Cell. Dev. Biol. Anim.: 2010, 46(8);664-72 PubMed 20535580
  7. Felicia Chen, Yuxia Cao, Jun Qian, Fengzhi Shao, Karen Niederreither, Wellington V Cardoso A retinoic acid-dependent network in the foregut controls formation of the mouse lung primordium. J. Clin. Invest.: 2010, 120(6);2040-8 PubMed 20484817
  8. Joseph Fawke, Sooky Lum, Jane Kirkby, Enid Hennessy, Neil Marlow, Victoria Rowell, Sue Thomas, Janet Stocks Lung function and respiratory symptoms at 11 years in children born extremely preterm: the EPICure study. Am. J. Respir. Crit. Care Med.: 2010, 182(2);237-45 PubMed 20378729
  9. M Solomon, H Grasemann, S Keshavjee Pediatric lung transplantation. Pediatr. Clin. North Am.: 2010, 57(2);375-91, table of contents PubMed 20371042
  10. Shinichi Abe, Masahito Yamamoto, Taku Noguchi, Toshihito Yoshimoto, Hideaki Kinoshita, Satoru Matsunaga, Gen Murakami, Jose Francisco Rodríguez-Vázquez Fetal development of the minor lung segment. Anat Cell Biol: 2014, 47(1);12-7 PubMed 24693478 | Anat Cell Biol.
  11. Cho-Ming Chao, Elie El Agha, Caterina Tiozzo, Parviz Minoo, Saverio Bellusci A breath of fresh air on the mesenchyme: impact of impaired mesenchymal development on the pathogenesis of bronchopulmonary dysplasia. Front Med (Lausanne): 2015, 2;27 PubMed 25973420 | Front Med (Lausanne).]]
  12. Hongwei Yu, Andy Wessels, Jianliang Chen, Aimee L Phelps, John Oatis, G Stephen Tint, Shailendra B Patel Late gestational lung hypoplasia in a mouse model of the Smith-Lemli-Opitz syndrome. BMC Dev. Biol.: 2004, 4;1 PubMed 15005800 | BMC Developmental Biology
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  14. Rachel S Kadzik, Ethan David Cohen, Michael P Morley, Kathleen M Stewart, Min Min Lu, Edward E Morrisey Wnt ligand/Frizzled 2 receptor signaling regulates tube shape and branch-point formation in the lung through control of epithelial cell shape. Proc. Natl. Acad. Sci. U.S.A.: 2014, 111(34);12444-9 PubMed 25114215 PMC4151720 | Proc Natl Acad Sci U S A.
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  19. Suzanne McGovern, Jie Pan, Guillermo Oliver, Ernest Cutz, Herman Yeger The role of hypoxia and neurogenic genes (Mash-1 and Prox-1) in the developmental programming and maturation of pulmonary neuroendocrine cells in fetal mouse lung. Lab. Invest.: 2010, 90(2);180-95 PubMed 20027181
  20. Pierre M Barker, Richard E Olver Invited review: Clearance of lung liquid during the perinatal period. J. Appl. Physiol.: 2002, 93(4);1542-8 PubMed 12235057
  21. Susan M Hall, Alison A Hislop, Sheila G Haworth Origin, differentiation, and maturation of human pulmonary veins. Am. J. Respir. Cell Mol. Biol.: 2002, 26(3);333-40 PubMed 11867341
  22. 22.0 22.1 Alison A Hislop Airway and blood vessel interaction during lung development. J. Anat.: 2002, 201(4);325-34 PubMed 12430957
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  24. 24.0 24.1 Cardoso WV, Kotton DN. Specification and patterning of the respiratory system. StemBook [Internet]. Cambridge (MA): Harvard Stem Cell Institute; 2008 Jul 16. PMID20614584 | StemBook - Specification and patterning of the respiratory system Cite error: Invalid <ref> tag; name "PMID20614584" defined multiple times with different content
  25. Thomas Volckaert, Alice Campbell, Erik Dill, Changgong Li, Parviz Minoo, Stijn De Langhe Localized Fgf10 expression is not required for lung branching morphogenesis but prevents differentiation of epithelial progenitors. Development: 2013, 140(18);3731-42 PubMed 23924632
  26. Esther Maier, Jonas von Hofsten, Hanna Nord, Marie Fernandes, Hunki Paek, Jean M Hébert, Lena Gunhaga Opposing Fgf and Bmp activities regulate the specification of olfactory sensory and respiratory epithelial cell fates. Development: 2010, 137(10);1601-11 PubMed 20392740
  27. Sophie M Thompson, Edwin C Jesudason, Jeremy E Turnbull, David G Fernig Heparan sulfate in lung morphogenesis: The elephant in the room. Birth Defects Res. C Embryo Today: 2010, 90(1);32-44 PubMed 20301217
  28. Yiming Xing, Changgong Li, Aimin Li, Somyoth Sridurongrit, Caterina Tiozzo, Saverio Bellusci, Zea Borok, Vesa Kaartinen, Parviz Minoo Signaling via Alk5 controls the ontogeny of lung Clara cells. Development: 2010, 137(5);825-33 PubMed 20147383
  29. Julia Norden, Thomas Grieskamp, Ekkehart Lausch, Bram van Wijk, Maurice J B van den Hoff, Christoph Englert, Marianne Petry, Mathilda T M Mommersteeg, Vincent M Christoffels, Karen Niederreither, Andreas Kispert Wt1 and retinoic acid signaling in the subcoelomic mesenchyme control the development of the pleuropericardial membranes and the sinus horns. Circ. Res.: 2010, 106(7);1212-20 PubMed 20185795


Michael Herriges, Edward E Morrisey Lung development: orchestrating the generation and regeneration of a complex organ. Development: 2014, 141(3);502-13 PubMed 24449833

David Warburton, Ahmed El-Hashash, Gianni Carraro, Caterina Tiozzo, Frederic Sala, Orquidea Rogers, Stijn De Langhe, Paul J Kemp, Daniela Riccardi, John Torday, Saverio Bellusci, Wei Shi, Sharon R Lubkin, Edwin Jesudason Lung organogenesis. Curr. Top. Dev. Biol.: 2010, 90;73-158 PubMed 20691848

Edward E Morrisey, Brigid L M Hogan Preparing for the first breath: genetic and cellular mechanisms in lung development. Dev. Cell: 2010, 18(1);8-23 PubMed 20152174

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S M Hall, A A Hislop, C M Pierce, S G Haworth Prenatal origins of human intrapulmonary arteries: formation and smooth muscle maturation. Am. J. Respir. Cell Mol. Biol.: 2000, 23(2);194-203 PubMed 10919986

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Pages where the terms "Historic Textbook" and "Historic Embryology" appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms and interpretations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Frazer JE. Development of the larynx. (1910) J Anat. 44: 156-191. PMID 17232839

Keibel F. and Mall FP. Manual of Human Embryology II. (1912) J. B. Lippincott Company, Philadelphia.

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