Lung Embryology
Sources: our notes, lecture ppt, High Yield Embryology, Langman’s embryology and
http://www.med.unc.edu/embryo_images/unit-welcome/welcome_htms/akgs.htm
Formation of the Lungs:
I.
Body Cavities form via lateral folding (day 19 - day 35ish(end of wk 4))
a. Intraembryonic coelem (body cavity) forms at the sides of the embryonic tri-laminar disc
by folding over of the amniotic cavity around the embryo and yolk sac.
b. Lateral mesoderm divides into somatic/parietal and splanchnic/visceral mesoderm
i. Pockets of polarized fluid transport create divisions of mesoderm
c. Surface ectoderm and gut tube endoderm become lined with serous membranes
d. At this time, the heart is forming on the dorsal thoracic coelem (not shown)
Day 19
Early wk4
Day 20
End of wk4
II.
Formation of the Mesenteries
a. When the intraembryonic coelem/cavity forms, the endoderm is separated, forming the
primitive gut tube
b. Ventral and dorsal connections of the gut tube to the embryo (dorsal) and coelem
(ventral) remain, becoming the mesenteries
c. The ventral mesentery disappears except for a remnant at the septum transversum
d. The septum transversum becomes the central tendon of the diaphragm and liver
1. The phrenic nerve (C3,C4,C5) innervates the diaphragm
2. The diaphragm, after formation, travels caudally, taking the phrenic
nerve with it.
Axial slice through the middle of the
embryo
Location of the ventral
mesentery/s. transversum
Midsagittal cut through the
length of the embryo
Another Midsagittal cut, with septum
transversum (orange) visible, as well as the liver
bud between it and the foregut. (27 days)
6wks/42 days, the septum transversum
separates the heart from the liver,
stomach and vitelline duct
III.
The intraembryonic coelem is divided into four cavities:
i. Peritoneal cavity- the septum transversum and the pleuroperitoneal folds
separate the thoracic (pleural/pericardial) cavities from the abdominal cavity
ii. Pericardial cavity– when the pleuropericardial folds fuse at midline, they leave
behind a separate pericardial cavity
iii. Two pleural cavities– created when the lungs bud from the foregut
1. Lung buds bulge into dorsal thoracic cavity
2. Pleuropericardial folds form as lateral outgrowths behind the heart
a. Contain cardiac veins
b. Contain phrenic nerve from septum transversum
c. Become the fibrous pericardium, where the phrenic nerve will
eventually reside
Axial view: pleuroperitoneal
folds and s. transversum
Longitudinal view on left, axial view higher
than septum transversum on right:
Pleuropericardial folds
IV.
Formation of the diaphragm
a. Separates the thoracic and abdominal/peritoneal cavities
b. Diaphragm is formed from
i. dorsal mesentery(esophagus and body wall)
ii. The septum transversum grows from the ventral mesentery/body wall dorsally
to the foregut (esophagus level) (grows posteriorly)
1. Closes off most of the space between the thoracic and abdominal
cavities
iii. 2 pleuroperitoneal folds close off the pericardioperitoneal canals left behind by
the growing septum transversum.
Wk6 (see s.transversum pic above),
with removal of the heart and future
diaphragm, shows lung buds cranial to
the stomach and pancreas.
V.
Lung Bud to Lung Formation
a. During wk 4, respiratory diverticula form in the ventral foregut between the 4th and 6th
pharyngeal arches
b. The respiratory diverticula become the lung bud
c. Lung bud -> 2 bronchial buds-> branch to primary/main bronchi, then secondary/lobar,
then tertiary/segmental bronchi, then subsegmental
i. The 2 bronchial buds form 3 primary bronchi on the right and 2 on the left.
d. The lung bud then becomes the trachea, the bronchial buds the bronchi
e. Loses connection to the mesoderm when the tracheoesophageal folds form
i. T.e. folds fuse at midline to separate the trachea(ventral) from the esophagus
(dorsal)
f. As the lungs bulge into the pleural canals/cavities, the splanchnic mesoderm around
them becomes the visceral pleura
i. NOTE: the splanchnic mesoderm INDUCES lung bud formation
ii. Candidate GFs: FGF-10, Wnt7b, bmp4, Shh
g. The walls of the pleural cavities’’ mesoderm (somatic mesoderm) becomes the parietal
pleura.
VI.
Stages of Lung Development
a. Wk 4-7 :embryonic stage
i. Lungs start to fill pleural cavities, primitive bronchi form
b. Wk8-16 pseudoglandular period/stage
i. Organ looks like a gland, lined with columnar cells
ii. Lung arteries form and follow the airways
c. Wk 17-24 :canalicular stage
i. Respiratory bronchioles form, columnar cells-> ciliated cuboidal
ii. Blood vessel formation continues with capillary ingrowth
d. Wk 24 to birth: terminal sac stage
i. Alveoli buds form and differentiate into Type I and Type II epithelia
ii. Surfactant is produced (measured by Lethicin: Sphingomyelin ratio – 2:1 is good)
iii. RDS-lack of surfactant
e. Birth to 8yrs of age: postnatal or alveolar period
i. 30million alveoli increase to 300 million in the mature lung
ii. Septation: growing alveoli are subdivided by septa such that the average size of
an alveolus remains constant.
VII.
When Lung Development Goes Wrong
a. Congenital Cystic Adenoid Malformation/Hamartoma
b. Failure of bifurcation of tracheoesophageal ridges