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.
Lung buds (stage 13)
Lungs (stage 22)
Fetal lung histology (Image: UWA Blue Histology)
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 respiratory motions and amniotic fliud are thought to have a role in lung maturation.
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).
Ross J. Metzger, Ophir D. Klein, Gail R. Martin, Mark A. Krasnow The branching programme of mouse lung development Nature 453, 745-750 (5 June 2008) doi:10.1038/nature07005
"we present the complete three-dimensional branching pattern and lineage of the mouse bronchial tree, reconstructed from an analysis of hundreds of developmental intermediates. ...propose that each mode of branching is controlled by a genetically encoded subroutine, a series of local patterning and morphogenesis operations, which are themselves controlled by a more global master routine."
Shu W, Lu MM, Zhang Y, Tucker PW, Zhou D, Morrisey EE. Foxp2 and Foxp1 cooperatively regulate lung and esophagus development. Development. 2007 May;134(10):1991-2000. (More? Respiratory Molecular Development)
Cardoso WV, Lu J. Regulation of early lung morphogenesis: questions, facts and controversies. Development. 2006 May;133(9):1611-24.
"During early respiratory system development, the foregut endoderm gives rise to the tracheal and lung cell progenitors. ....Here, we review early stages in lung development and highlight questions and controversies regarding their molecular regulation."
Harris KS, Zhang Z, McManus MT, Harfe BD, Sun X. Dicer function is essential for lung epithelium morphogenesis. Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2208-13.
"DICER is a key enzyme that processes microRNA and small interfering RNA precursors into their short mature forms, enabling them to regulate gene expression. Only a single Dicer gene exists in the mouse genome, and it is broadly expressed in developing tissues. Dicer-null mutants die before gastrulation.......leading us to propose that Dicer plays a specific role in regulating lung epithelial morphogenesis independent of its requirement in cell survival."
UNSW Embryology: Pig Stage 13/14 Overview | Stage 13/14 Embryo (Pig) | Stage 22 Embryo (Human) | Selected Stage 22 Human high power (st22) | Early Fetal (wk10) | Systems (Pig, Respiratory) | Read Respiratory Development- Selected Review 1999 Abstracts
Embryo Images Unit: Unit: Body Cavities
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.
Splanchnic Mesoderm (mesenchyme)
Human Airway Development
Am J Physiol Lung Cell Mol Physiol 2002 Special Edition - Pre- and Postnatal Lung Development, Maturation, and Plasticity
Cardoso WV, Lu J. Regulation of early lung morphogenesis: questions, facts and controversies. Development. 2006 May;133(9):1611-24.
Warburton D, Bellusci S, De Langhe S, Del Moral PM, Fleury V, Mailleux A, Tefft D, Unbekandt M, Wang K, Shi W. [See Related Articles] Molecular mechanisms of early lung specification and branching morphogenesis. Pediatr Res. 2005 May;57(5 Pt 2):26R-37R.
Kumar VH, Lakshminrusimha S, Abiad MT, Chess PR, Ryan RM. [See Related Articles] Growth factors in lung development. Adv Clin Chem. 2005;40:261-316. Review.
[No authors listed] [See Related Articles] Surfactant replacement therapy for respiratory distress syndrome. American Academy of Pediatrics. Committee on Fetus and Newborn. Pediatrics. 1999 Mar;103(3):684-5.
O'Rahilly R, Tucker JA. [See Related Articles] The early development of the larynx in staged human embryos. I. Embryos of the first five weeks (to stage 15). Ann Otol Rhinol Laryngol. 1973 Sep-Oct;82:1-27.
Dilly SA. Scanning electron microscope study of the development of the human respiratory acinus. Thorax. 1984 Oct;39(10):733-42. PMID: 6495241
Selected Lists of References from PubMed March 1999 search results are available for Department of Anatomy computers without internet access. Computers with internet access can search from either Selected Research Articles and Reviews | Respiratory/development/review/5year limit" | "Lung development/review/5year limit"
alveolar - (Latin, alveus = cavity or hollow) Term used in relation to the alveoli of the lungs. The final functional sac of the respiratory tree where gas exchange occurs between the alveolar space and the pulmonary capillaries.
alveolar stage - (Latin, alveus = cavity or hollow) Term used to describe the final histological/developmental stage (Pseudoglandular, Fetal Canalicular, Terminal sac, Alveolar) of lung development. This stage occurs from late fetal/neonate. The final functional sac of the respiratory tree exists, where gas exchange occurs between the alveolar space and the pulmonary capillaries.
alveolar duct - respiratory tract that in the adult has alveoli opening into it and has no cuboidal epithelium.
atmospheric pressure - Term describing the pressure of the air outside of the body.
atresia - (Greek, a = without + tresis = perforation) Term used for anatomical closing or absence of a cavity or opening that should exist. Used as an antomical, pathological and clinical term: esophageal atresia, biliary atresia, duodenal atresia, jejunal atresia, choanal atresia, urethral atresia, bronchial atresia.
canalicular stage - (fetal canalicular, canalicular phase) Term used to describe lung development, after early embryonic the second of the histological/developmental stages (Pseudoglandular, Fetal Canalicular, Terminal sac, Alveolar). This stage occurs during the fetal period from week 16 to 24. During this stage there is lung bud mesenchymal angiogenesis and cellular differentiation into different stromal cell types (fibroblasts, myoblasts and chondrocytes).
ciliated pseudostratified columnar epithelium - forms mucous membrane that lines the trachea and the nasal cavity and nasopharynx epithelium.
ductus arteriosus - A vascular shunt between the pulmonary artery and descending aorta, which allows fetal right heart output (most, 88%) to go to systemic circulation. This shunt closes normally at birth.
elastic theory - The hypothesis that lung acinar development during the saccular stage is guided by the preprogrammed location of a surrounding elastic network.
epiglottis - (Greek, epi = above, upon) cartilaginous part of the larynx above the glottis, which in infancy directs food into the esophagus and not the trachea. Embryologically develops in the foregut from the hypobranchial eminence. Postnatal anatomical development in humans involves a maturational descent in infancy (4 and 6 months of age). Contains lymphoid tissue (larynx-associated lymphoid tissue, LALT and Bronchus-associated lymphoid tissue, BALT). (More? Respiratory Notes | Gastrointestinal Tract Notes)
expiration - (exhalation) The process of letting air out of the lungs during the breathing cycle. Due to the combination of relaxation of the diaphragm and elastic recoil of tissue decreases the thoracic volume and increases the intraalveolar pressure.
fistula - An abnormal communication between 2 structures (organs, vessels, cavities) that do not normally connect. (More? Respiratory Abnormalities)
hypopharyngeal eminence - (hypobranchial eminence) An early embryonic structure in the developing head. A narrow midline mesodermal (mesenchymal) exension lying within the floor curve of the developing pharynx. Fusion of 3rd pharyngeal arches and precursor of root of tongue. Early developing thyroid cells also migrate into this structure as cords of cells. (More? Head Notes | Endocrine Development - Thyroid)
hyaline cartilage - type of cartilage located in the tracheal wall to provide support and prevent the trachea from collapsing. Note that the tracheal wall has a region of posterior soft tissue to allow for expansion of the esophagus, which is immediately posterior to the trachea.
inspiration - (inhalation) The process of taking air into the lungs. Due to diaphragm contraction and the thoracic cavity increasing in volume. This decreases the intraalveolar pressure leading to air flows into the lungs.
intraalveolar pressure - Term describing the pressure inside the alveoli of the lungs, which changes during inspiration and expiration.
intrapleural pressure - Term describing the pressure within the pleural cavity.
laryngopharynx - (hypopharynx) The portion of the pharynx that extends from the hyoid bone down to the lower margin of the larynx.
laryngotracheal groove - Early embryonic foregut developmental feature, forms on the anterior (ventral) wall of pharynx and gives rise to larynx, trachea, respiratory tree. (More? Respiratory Notes | Head Notes | Stage 13/14 Embryo Section B3 Section B4)
larynx - Site of the the vocal folds in the neck below the division of pharynx into the trachea and the esophagus. Embryologically develops from the foregut with the lining derived from endoderm and the cartilage from pharyngeal arch 4 and 6. Beginning as a simple foregut groove, the laryngotracheal groove which folds to form the laryngotracheal bud, then the larynx and trachea.
lung bud - The term describing the primordia of lung development. Foregut endoderm branches into the surrounding visceral mesoderm, forming the trachea, which brances again into the bronchi and thsi process is repeated over and over again through development. Establishing the major respiratory branches first, followed by minor branches, then terminal branches, then immature alveoli which later mature to form teh functional end structures of the lung.
nasopharynx - The portion of the pharynx posterior to the nasal cavity and extends inferiorly to the uvula.
oropharynx - The portion of the pharynx that is posterior to the oral cavity.
paranasal sinuses - Air-filled cavities surrounding the nasal cavity and open into it, which combine in function to: reduce skull weight, produce mucus, and act as resonating chambers affecting voice quality. Located within in the frontal, maxilae, ethmoid, and sphenoid bones with the same name as the bones in which they are located.
parietal pleura - Forms the outer lining of pleural cavity. Mesoderm of the thoracic cavity body wall and derived from epithelia of pericardioperitoneal canals from intraembryonic coelom. The other inner pleural layer is the visceral pleura (splanchnic mesodermal in origin).
pharynx - (throat) Forms the initial segment of the upper respiratory tract divided anatomically into three regions: nasopharynx, oropharynx, and laryngopharynx (hypopharynx). Anatomically extends from the base of the skull to the level of the sixth cervical vertebra.
pleura - A double-layered serous membrane enclosing each lung. Visceral pleura layer is firmly attached to the surface of the lung. Parietal pleura layer lines the wall of the thorax. At the lung hilum, the visceral pleura is continuous with the parietal pleura. The pleural cavity between the visceral and parietal pleurae contains a thin film of serous fluid that is produced by the pleura.
pleural cavity - Anatomical body cavity in which the lungs develop and lie. The pleural cavity forms in the lateral plate mesoderm as part of the early single intraembryonic coelom. This cavity is initially continuous with pericardial and peritoneal cavities and later becomes separated by folding (pleuropericardial fold, pleuroperitoneal membrane) and the later formation of the diaphragm. The pleural cavities form initially as two narrow canals. Note the single intraembryonic coelom forms all three major body cavities: pericardial, pleural, peritoneal. (More? Coelomic Cavity Notes)
pleural fluid - A thin film of serous fluid that is produced by the pleura layers and acts as a lubricant, reducing the friction as the two layers slide against each other, and also helps to hold the two layers together as the lungs inflate and deflate.
pleuropericardial fold - (pleuropericardial membrane) An early embryonic fold which restricts the communication between pleural cavity and pericardiac cavity, contains both the cardinal vein and phrenic nerve.
pleuroperitoneal membrane - An early embryonic membrane that forms inferiorly at the septum transversum to separate peritoneal cavity from pleural cavity. (More? Coelom Notes)
radial alveolar count - The number of alveoli between respiratory bronchioles and the end of the acinus, a measurement used in postnatal lung growth.
respiratory bronchiolus - respiratory tract in the adult which has alveoli opening into it and has part of the wall lined by ciliated epithelium. In the canalicular period it is lined by flattened epithelium, which then becomes a mixture of flattened and cuboidal epithelium during the terminal sac period.
sacculation - A general anatomical term meaning to formed a series of sac-like expansions. In lung development, the term refers to the process of lung epithelial cell differentiation, vascular remodeling and thinning of the mesenchyme. This process leads to enlargement of the diameter and surface area of the alveolar sacs. Distal epithelial cells form 2 populations: 1. cells flattens, thins, and spreads to form type I cells; 2. cells remain cuboidal, acquire surfactant filled lamellar bodies and differentiate into type II cells.
saccule - respiratory tract that forms a large, thin walled air space lined by flattened epithelium (28 weeks to 2 months after birth).
septum transversum - (transverse septum) A mesodermal region in the early embryo. Identified externally as the junctional site between amnion and yolk sacs, and internally (within the embryo) lying directly beneath the heart and at the foregut/midgut junction. This ventro-dorsal "plate" of mesoderm contributes several structures including: the central tendon of diaphragm and some of the liver. The transverse septum has an important structural role in early embryonic development and is pierced by the gastrointestinal tract.
surfactant - a detergent secreted by Type 2 alveolar cells between alveolar epithelium. Functions to lower surface tension, allowing lungs to remain inflated. Note: In humans, these cells and their secretion develop towards the very end of the third trimester, just before birth. Hence the respiratory difficulties associated with premature births (Newborn Respiratory Distress Syndrome, Hyaline membrane disease). (More? Respiratory Abnormalities | Newborn Respiratory Distress Syndrome)
terminal bronchiolus - respiratory tract forming the last airway before a respiratory bronchiolus.
terminal sac stage (terminal sac phase) Term used to describe fetallung development (late fetal week 24 to 36) the second last histological/developmental stage (Pseudoglandular, Fetal Canalicular, Terminal sac, Alveolar). During this stage branching and growth of the terminal sacs occurs, with cellular differentiation of the type -II pneumonocytes and type - I pneumonocytes. The final functional sac of the respiratory tree occurs at the next neonatal period, where gas exchange occurs between the alveolar space and the pulmonary capillaries.
transitional duct - respiratory tract lined by flattened epithelium, which connects the respiratory bronchiolus to the saccules during the terminal sac period. This structure later forms the alveolar duct.
Waldereyer's Ring - Term used to describe the pharyngeal, palatine, and lingual tonsils which are located in the pharynx.