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 mesodermc. Surface ectoderm and gut tube endoderm become lined with serous membranesd. At this time, the heart is forming on the dorsal thoracic coelem (not shown)

Day 19 Day 20

Early wk4 End of wk4

II. Formation of the Mesenteriesa. When the intraembryonic coelem/cavity forms, the endoderm is separated, forming the

primitive gut tubeb. Ventral and dorsal connections of the gut tube to the embryo (dorsal) and coelem

(ventral) remain, becoming the mesenteriesc. The ventral mesentery disappears except for a remnant at the septum transversumd. The septum transversum becomes the central tendon of the diaphragm and liver

1. The phrenic nerve (C3,C4,C5) innervates the diaphragm2. The diaphragm, after formation, travels caudally, taking the phrenic

nerve with it.

Axial slice through the middle of the embryo

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)

Location of the ventral mesentery/s. transversum

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 cavityii. Pericardial cavity– when the pleuropericardial folds fuse at midline, they leave

behind a separate pericardial cavityiii. Two pleural cavities– created when the lungs bud from the foregut

1. Lung buds bulge into dorsal thoracic cavity2. Pleuropericardial folds form as lateral outgrowths behind the heart

a. Contain cardiac veinsb. Contain phrenic nerve from septum transversumc. Become the fibrous pericardium, where the phrenic nerve will

eventually reside

6wks/42 days, the septum transversum separates the heart from the liver, stomach and vitelline duct

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 diaphragma. Separates the thoracic and abdominal/peritoneal cavitiesb. 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

cavitiesiii. 2 pleuroperitoneal folds close off the pericardioperitoneal canals left behind by

the growing septum transversum.

V. Lung Bud to Lung Formationa. During wk 4, respiratory diverticula form in the ventral foregut between the 4 th and 6th

pharyngeal archesb. 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 subsegmentali. 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 bronchie. 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 formationii. Candidate GFs: FGF-10, Wnt7b, bmp4, Shh

g. The walls of the pleural cavities’’ mesoderm (somatic mesoderm) becomes the parietal pleura.

Wk6 (see s.transversum pic above), with removal of the heart and future diaphragm, shows lung buds cranial to the stomach and pancreas.

VI. Stages of Lung Developmenta. Wk 4-7 :embryonic stage

i. Lungs start to fill pleural cavities, primitive bronchi formb. Wk8-16 pseudoglandular period/stage

i. Organ looks like a gland, lined with columnar cellsii. Lung arteries form and follow the airways

c. Wk 17-24 :canalicular stagei. Respiratory bronchioles form, columnar cells-> ciliated cuboidal

ii. Blood vessel formation continues with capillary ingrowthd. Wk 24 to birth: terminal sac stage

i. Alveoli buds form and differentiate into Type I and Type II epitheliaii. Surfactant is produced (measured by Lethicin: Sphingomyelin ratio – 2:1 is good)

iii. RDS-lack of surfactante. Birth to 8yrs of age: postnatal or alveolar period

i. 30million alveoli increase to 300 million in the mature lungii. Septation: growing alveoli are subdivided by septa such that the average size of

an alveolus remains constant.

VII. When Lung Development Goes Wronga. Congenital Cystic Adenoid Malformation/Hamartomab. Failure of bifurcation of tracheoesophageal ridges