Lung buds from a human embryo of about four weeks, showing commencing lobulations.
Lungs of a human embryo more advanced in development.
|Precursor||Ventral part of the Foregut|
In the fourh week of development, the respiratory bud starts to grow from the ventral (front) side of the midforegut into the mesoderm that surrounds it, taking the form of a pouch. Around the 28th day, two lung buds develop on the sides of the distal part of the respiratory bud and begin to grow laterally, expanding into the primitive pleural cavity.
The molecular signaling involved in the specification of the respiratory bud starts with the expression of the Nbx2-1 gene, which determines the respiratory field, the area where the respiratory bud will begin to grow from. The signaling that makes the growth of the respiratory bud possible is complex and involves a number of interactions between the mesoderm and the respiratory bud epithelium, in which members of the Fgf and Fgfr family of genes express.
Separation of trachea and esophagus
At first, the posterior part of the trachea is open to the esophagus, but as the bud elongates two longitudinal mesodermal ridges begin to form and grow until they join, forming a wall between the two organs. An incomplete separation of the organs leads to a congenital abnormality known as a tracheoesophageal fistula.
The epithelium of the larynx is of endodermal origin, but the laryngeal cartilages, unlike the rest of the respiratory bud connective tissue, come from the mesenchyme of the fourth and sixth pharyngeal arches. The fourth pharyngeal arch, adjacent to what will be the root of the tongue, will become the epiglottis. The sixth pharyngeal arch, located around the laryngeal orifice, will become the thyroid, cricoid and arytenoid cartilages. These structures are formed in a process in which the lining cells of the primitive larynx proliferate and occlude it. Later, it recanalizes leaving two membrane-like structures: the vocal folds and the vestibular folds. In between, an enlarged space, the ventricle, remains. Failure in this process leads to a serious but rare condition called congenital atresia of the larynx.
After the lung buds have formed, they begin to grow and branch forming a primitive version of the bronchial tree, determining how the lobes of the lung will be arranged in the mature organ. The first stage of alveolar development, spanning between the fifth and the 16th week of development, is called the pseudoglandular stage. It is so called because of the histological appearance of the primitive alveoli, which resemble glandular tissue. After the pseudoglandular stage, the lung enters the canalicular and saccular phases. During these stages, the terminal tubes narrow and give rise to small saccules, which become increasingly associated with capillaries as to make gas exchange possible. The alveolar epithelium begins to differentiate into two distinct types of cells: type I pneumocytes and type II pneumocytes, as well as the respiratory epithelium of the trachea and bronchial tree.
- Sadler, Thomas W. (2012). Langman's Medical Embryology. Lippincott Williams & Wilkins. ISBN 978-14-51113-42-6.
- Cardoso, W.V. and Kotton, D.N., Specification and patterning of the respiratory system (July 16, 2008), StemBook, ed. The Stem Cell Research Community, StemBook, doi/10.3824/stembook.1.10.1
- Smith II, Bain AD. (1965). "Congenital atresia of the larynx" (PDF). Annals of Otology, Rhinology and Laryngology 74 (2): 338–349. doi:10.1177/000348946507400205.
- Phases of lung development
- Morrisey EE, Hogan BL (2010). "Preparing for the first breath: genetic and cellular mechanisms in lung development.". Developmental Cell 18 (1): 8–23. doi:10.1016/j.devcel.2009.12.010. PMC 3736813. PMID 20152174.
- respiratory+diverticulum at eMedicine Dictionary
- digest-012a — Embryo Images at University of North Carolina
- digest-013 — Embryo Images at University of North Carolina
- Swiss embryology (from UL, UB, and UF) rrespiratory/phasen02
- Histology at med.unsw.edu.au
- Diagram at chronolab.com