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Time
30 hrs after
fertilization
Events
Zygote undergoes first cleavage to become a 2 cell embryo.
Later, with further cell divisions, forming 4-, 8-cell pre-embryo.
Day 4 (72 80
hours after
fertilization)
Day 5 (96
hours after
fertilization)
Day 6 (120
hours after
fertilization)
Day 7
(150 hours
after
fertilization)
Implantation begins;
As soon as blastocyst attaches to the endometrium
epithelium:
Day 8
(168 hours
after
fertilization)
Day 9
Day 10
Day 12
Late Day 12
Day 13
Day 14
Day 15 - 16
Gastrulation occurs:
Epiblast cells near the primitive streak proliferates and migrates through
the primitive streak.
The first cells will begin to replace the hypoblast to later form the
endoderm.
The remaining cells form intra-embryonic mesoderm between the other
two layers and produce two midline structures between the epiblast and
the future endoderm: the prechordal plate and the notochordal process.
Day 17
Day 18
Pre-embryo: In humans, pre-embryo refers to the product of gametic union after the completion of fertilization to the completion of implantation about the end of the
second week (more strictly speaking and correct: the appearance of the primitive streak).
The preembryonic forms ranges from the zygote, morula, blastocyst, bilaminar embryonic disc to the appearance of the primitive streak. That is, the term pre-embryo is
used to refer to the first three major stages of development: the earliest stages of cell division (the so called cleavage stages), the blastocyst (when the pre-embryo is a
hollow ball of cells) and the stages of implantation up to the formation of the primitive streak.
Embryo: In humans, embryo refers to the product of gametic union after the completion of implantation about the end of the second week (more strictly speaking and
correct: the appearance of the primitive streak) to the completion of organogenesis (about the end of the eighth week from gametic union). That is, after the process of
implantation is completed, we have an embryo.
Fetus: In human, fetus refers to the product of gametic union after completion of organogenesis (start of the ninth week) to birth. That is, completion of organogenesis is
used to signal the transition from embryo to fetus. In other words, the accomplishment of organogenesis ends the period during which the developing organism is called an
embryo and begins the period in which the organism is called a fetus.
In the fetal stage, all organs (except reproductive system) do not undergo new formation, they simply undergo fine differentiation and rapid cell growth.
Newborn (aka neonate): In medical contexts, newborn or neonate (from Latin,neonatus, newborn) refers to an infant in the first 28 days after birth;
Infant: young children between the ages 1 month and 12 months;
Toddler: when a human child learns to walk.
In the middle of week 3 [day 17 and day 18], blood islands appears extraembryonically and
intraembryonically as red spots in 3 locations, with extraembryonic vasculogenesis slightly
preceding intraembryonic vasculogenesis.
On day 17-18, the mesoderm layer differentiates into paraxial mesoderm, intermediate mesoderm
and lateral plate mesoderm.
In the 3rd week, shortly after the appearance of blood islands, the blood islands begin to develop
into blood vessels of the primitive cardiovascular system.
Blood vessels formed include:
A pair of vitelline veins that return blood from the yolk sac
A pair of umbilical veins that return blood from the chorion via the connecting stalk
Chorionic vessels
Paired endocardial tubes
Paired dorsal aortae
In particular the endocardial tubes and dorsal aortae are formed on day 19.
On day 18-19, coelomic spaces/intercellular spaces form in the lateral plate mesoderm, thus dividing the lateral plate
mesoderm.
On day 20, paired dorsal aortae connect with the rostral ends of the paired endocardial tubes. Shortly after, the connection
of dorsal aortae with the endocardial tubes (still on day 20), embryonic folding begins, bringing the bilateral endocardial
tubes toward the ventral midline of the embryo. On day 20, the septum transversum also begins to form. On day 20,
coelomic spaces in the lateral plate mesoderm merges to form the intraembryonic coelom.
A number of events happen by the end of the third week [day 21]:
Embryonic folding which began on day 20 continues to fold on day 21 (folding is complete by
day 28). The embryo folds longitudinally so that the heart ends up in the future thorax region.
While lateral folding brings the endocardial tubes together in the midline.
By day 21, the paired endocardial tubes, the paired dorsal aortae and blood vessels in the
connecting stalk, chorion, and yolk sac are linked up, forming a primitive cardiovascular
system. In general, new vessels that will arise later, do so as outgrowths of these existing
vessels.
On day 21 22, when the dorsal aortae are still paired, three sets of arterial branches begin
to sprout from the paired dorsal aortae:
o Ventral branches: including the series of paired vitelline arteries and a pair of
umbilical arteries
o Dorsolateral branches (aka intersegmental branches): a series of paired arteries
arising from the postero-lateral surface of the dorsal aortae.
o Lateral branches: a series of paired arteries
A series of constrictions and dilations appears. These will later become truncus arteriosus,
bulbus cordis, primitive ventricle, primitive atria, sinus venosus (after completion of fusion)
on day 22.
The primitive heart may begin to beat on day 21 - 22. This may occur even before the heart
tubes are completely fused together.
On day 22, fusion of the endocardial tubes complete (thus forming the primitive heart tube). The series of
constrictions and dilations now (day 22) form the truncus arteriosus, bulbus cordis, primitive ventricle,
primitive atria, sinus venosus.
Endodermal lining on the ventral side of the caudal foregut differentiates into hepatoblast and
begins to proliferate to form a thickening called the hepatic plate on day 22.
The anterior cardinal veins and posterior cardinal veins appear on about day 22 day 24. The
anterior cardinal veins and the posterior cardinal veins join to form the left and right common
cardinal veins that drain into the sinus venosus around day 24 day 26 (cardinal system is thus
formed).
The paired dorsal aorta begins migrate toward each other to fuse on day 23 - 25. And on day 25 28, the paired dorsal aorta have fused together caudally from the tenth to sixteenth somite,
forming in the region of fusion a single dorsal aorta (median dorsal aorta), which will later become
the descending aorta of the adult.
As the left and right dorsal aortas begins to fuse, the paired vitelline arteries will begin to fuse as
well. By day 25 - 28, the paired vitelline arteries have fused and become unpaired. Most vitelline
arteries will begin to degenerate over time. Around day 35 (near the end of the fifth week), only 3
unpaired vitelline arteries persists and they are called: the celiac trunk (to the foregut), the
superior mesenteric artery (to the midgut) and the inferior mesenteric artery (to the hindgut).
Meanwhile (around the time where the aortic arches are reforming at the cephalad end which is
also around the time where the vitelline arteries are remodelling), lateral arterial branches and
intersegmental arteries (dorsolateral arterial branches) that were formed previously are being
further developed.
Looping and elongation of the primitive heart tube begins on day 23 (and completes on day 28).
The connection between the dorsal aortae and the paired endocardial tubes are being pulled
during embryonic folding until they form a loop called the first aortic arch on day 24 (3mm). In
other words, the first pair of aortic arches has formed on day 24 (3mm).
Note: The three vitelline segments that persist are the 10th,
13th and 21st.
Note: By the end of day 26, the basic fetal vascular system is
almost complete.
On day 28, folding completes. Also on day28, the ventral mesentery degenerates resulting the merging of
right and left parts of the intraembryonic coelom (body wall closure). The midgut is now suspended from
the abdominal wall only by the dorsal mesentery. Note that the midgut is continuous with the yolk sac via
the vitelline duct.
On day 24, the cervical portions of the internal carotid arteries (aka primitive internal carotid
artery) have emerged from the first aortic arch.
On day 28, intracranial portions of the internal carotid arteries have developed by the extension
of the dorsal aortae. That is, the dorsal aortae have extended cranially to form the intracranial
portions of the primitive internal carotid arteries.
On day 28, a pair of longitudinal neural arteries have developed from the primitive vascular
plexus on the surface of the neural tube. The pair of longitudinal neural arteries are located
dorsal and parallel to the internal carotid artery. Note: The longitudinal neural arteries are initially
supplied from below by the dorsal aortae via the transient cervical intersegmental arteries (first
intersegmental cervical C1 artery?).
Note: first intersegmental cervical C1 artery is also known as the proatlantal intersegmental artery.
On day 28 29, other transient connections between each longitudinal neural artery and its
corresponding carotid artery also develop. These are the primitive trigeminal arteries, the
primitive otic arteries, and the primitive hypoglossal arteries.
On day 29 30, recall that both the first and second aortic arches have regressed. Thus the
primitive internal carotid arteries now appear as extensions of the third aortic arch.
On day 29 30, shortly after the involution of the first and second aortic arches, the rostral
(distal) end of the internal carotid arteries have developed cranial (rostral) and caudal divisions.
Note: The cranial division initially terminates as olfactory arteries whereas the caudal division
initially forms an anastomosis (second temporary connection) between the internal carotid
arteries and the dorsal longitudinal neural arteries. The portion of the anastomosis that joins to
the cranial end of the dorsal longitudinal artery will later give rise to the posterior communicating
arteries. The remaining portion of the anastomosis typically later regresses and disappears.
On day 31 32, primitive maxillary arteries and primitive dorsal opthalamic arteries have
developed as branches of the internal carotid arteries.
On day 31 32, ventral pharyngeal arteries have developed as extensions of the third aortic arch.
On day 31 32, subsequent to the development of the posterior communicating arteries, the
primitive connections (primitive trigeminal arteries, the primitive otic arteries, and the primitive
hypoglossal arteries) between the internal carotid arteries and the longitudinal neural arteries
begin to regress. The otic artery regresses first, followed by the hypoglossal artery, and lastly the
trigeminal artery. These primitive connections have regressed in the period between day 32 day 35.
Note: Blood in this period reaches the longitudinal neural arteries via the posterior communicating
arteries and the proatlantal intersegmental arteries. The proatlantal intersegmental artery becomes the
major blood supply to the posterior circulation until the definitive vertebral arteries form.
On day 32 33, vertebral arteries begin to form from longitudinal anastomoses of the cervical
intersegmental arteries.
On day 33, the longitudinal neural arteries have joined to form a single median artery called the
basilar artery. Note: the caudal region remains plexiform and is later replaced by the inferior
cerebellar arteries.
On day 35 36, vertebral arteries have formed from the longitudinal anastomoses of the cervical
intersegmental arteries. While the portions of the first six cervical intersegmental arteries, that
are connected to the dorsal aortae, begin to regress. In particular, the proatlantal
intersegemental arteries have regressed around day 36 37.
Note: The portion of the proatlantal intersegmental artery that remain contributes to the
horizontal segment (V3) of the vertebral artery.
On day 35 36, the common carotid arteries begin to form as the segments of dorsal aortae
between 3rd and 4th aortic arches (known as the carotid ducts) begin to regress.
On day 37 38, anterior cerebral arteries, middle cerebral arteries, posterior cerebral arteries
and anterior choroidal arteries have formed (begins to form on day 33 - 35??).
Note: The anterior cerebral arteries, middle cerebral arteries and anterior choroidal arteries
develop from the rostral/cranial division of the internal carotid arteries. On the other hand, the
posterior cerebral arteries arise from the basilar arteries.
On day 38 - 39, the ventral pharyngeal arteries have become the external carotid arteries.
On day 38 39, the distal part of the right sixth arch begins to disappear.
Around day 40, the vertebral arteries finish their maturation. The remnants of the portions of the
first six cervical intersegmental arteries, that are connected to the dorsal aortae, are barely visible
by this time.
On day 42, the segments of dorsal aortae between the 3rd and 4th aortic arches becomes much
thinner.
On day 42, the distal part of the right sixth aortic arch has disappeared while the proximal part
has formed the right pulmonary artery. That is, the right sixth aortic arch has lost its connection
with the right dorsal aorta.
On day 42 44, plexiform anastomoses have developed across the midline that join the anterior
cerebral arteries. This will later give rise to the anterior communicating artery.
On day 44, the segments of dorsal aortae between the 3rd and 4th aortic arches have disappeared.
The common carotid arteries now exist as stems of the internal and external carotid arteries.
On day 45 - 46, the distal portion (the segment between the origin of the seventh intersegmental
artery and the junction with the left dorsal aorta) of the right dorsal aorta begins to disappear.
Note: the proximal portion will later remains as part of the right subclavian artery.
Around day 48 - 49, the vertebral arteries have shifted to its adult position. The cervical intersegmental arteries are obliterated, with the exception of the 7th inter-segmental artery, which
gives rise to the subclavian artery.
Around day 48 49, external carotid continues to elaborate with branches for thyroid, lingual,
occipital and external maxillary arteries. The more proximal portion of this system displays the
primordial internal maxillary artery which will eventually become the middle meningeal artery.
On day 49 51, anterior communicating arteries have developed and the circle of Willis is
formed. Note: the Circle of Willis is completed with the formation of the anterior communicating
artery.
On day 51, the distal portion (the segment between the origin of the seventh intersegmental
artery and the junction with the left dorsal aorta) of the right dorsal aorta have disappeared. The
proximal portion has formed part of the right subclavian artery.
NOTE
The basilar system, including stems of the anterior inferior cerebellar arteries and posterior inferior
cerebellar arteries with small vessels extending into the developing choroid plexus of the fourth ventricle,
can be visible by CS 18 19 although I cannot find conclusive information on exactly when and in what
order these arteries are formed. Some clues include: (i) At day 35, the only blood supply to the
cerebellum is from the superior cerebellar arteries. It is not until day 44 that the PICA (posterior inferior
cerebellar arteries) become apparent. (ii) The anterior inferior cerebellar arteries arise just after the
longitudinal neural arteries have united to form the basilar artery.
Note:
AICA = anterior inferior cerebellar artery = anterior and inferior cerebellar artery.
PICA = posterior inferior cerebellar artery = posterior and inferior cerebellar artery.
On day 29 30, the left and right subcardinal veins have developed and have connected to each
other by a median anastomosis (intersubcardinal anastomosis) in front of the aorta.
On day 34 38, the left and right subcardinal veins have formed lateral anastomoses with the
posterior cardinal veins (postcardinal-subcardinal anastomosis).
On day 34 38, the right subcardinal vein has obtained access to the liver where a critical
anastomosis (the hepatosubcardial junction) develops between the right subcardinal vein and the
hepatic sinusoids. This initially small anastomosis will later (eventually) enlarges to become
portion of the inferior vena cava.
On day 36 40, after the formation of the hepatosubcardial junction, the hepatic sinusoids form
a large posterior channel within the liver, which becomes the intrahepatic portion of the inferior
vena cava.
On day 38 40, the left and right supracardinal veins begins to sprout from the posterior cardinal
vein, developing parallel (dorsolateral) to the posterior cardinal vein and running medial to the
subcardinal vein.
On day 40 - 42, the left and right supracardinal veins are formed. These veins are connected
proximally with the intersubcardinal anastomosis via the supracardinal-subcardinal anastomosis.
Note: Distally the supracardinal veins will later join the interpostcardinal anastomosis when it the
interpostcardinal anastomosis is formed.
On day 40 42, the posterior cardinal veins begin to regress in the middle, whereas the distal
posterior cardinal veins begin develop a weblike anastomosis (interpostcardinal anastomosis).
On day 40 42, the subcardinal veins begins remodelling: The longitudinal segments of the left
subcardinal vein begins to regress while the right subcardinal vein begins to lose its connection
with the posterior cardinal vein. Note: This will result in the left side of the body served by the
subcardinal system drain solely through transverse anastomic channels to the right subcardinal
vein.
On day 42 45, interpostcardinal anastomosis has formed distally and has been joined by the
supracardinal veins.
On day 45 49, the posterior cardinal veins have nearly completely regressed with the exception
of the cranial and caudal (cephelad to the interpostcardinal anastomosis) extent that persists.
On day 45 49, a brachiocephalic anastomosis has formed between the left and right anterior
cardinal vein.
On day 50 54, different segments of IVC has now fully developed from the vitelline, subcardinal
and supracardinal veins.
The hepatocardiac segment of IVC (the portion between the liver and the heart) is
derived from the right vitelline vein (right hepatocardiac channel).
Hepatic segment of IVC is developed from the hepatic sinusoids.
Suprarenal segment of IVC (above the kidneys) is formed from the right subcardinal vein.
Renal segment of IVC is formed from the right supracardinal-subcardinal anastomosis.
Infrarenal segment of IVC (portion of the IVC distal to the entrance of the renal veins) is
formed from the right supracardinal vein.
On day 50 54:
The junction for the renal, adrenal and gonadal veins is developed from the
intersubcardinal anastomosis.
The renal veins are also formed from the intersubcardinal anastomosis. Some sources
suggest that the left and right supracardinal-subcardinal anastomoses may also be
involved.
The gonadal veins are formed from the remnants of parts of the subcardinal veins below
the intersubcardinal anastomosis.
The suprarenal veins are formed from the remants of parts of the subcardinal veins above
the intersubcardinal anastomosis.
An anastomosis forms below the liver between the two supracardinal veins out of which
a part of the hemiazygos vein will later arise. The supracardinal veins give rise to the
azygous and hemiazygos veins.
On day 52 56, the superior vena cava develops from the union of the proximal right anterior
cardinal vein and the right common cardinal vein.
On day 32, Perforations/fernestrations appear in the septum primum before closure of foramen
primum.
On about day 33 day 35, the perforations/fernestrations have coalesced to form foramen
secundum. Concurrently or immediately after that, still on day 33 to day 35, the septum primum
merges with the endocardial cushions resulting in the closure of foramen primum. Also
concurrently or immediately after, septum secundum begins to develop to the right of the
adjacent septum primum.
The septum secundum grows downward and will soon cover/overlap/overlie the foramen
secundum on its right side but never forms a complete atrial partition. It forms an incomplete
partition. The process of septum secundum development leaves a foramen at about the midpoint
of the septum secundum.
On about day 37 - 42, the septum secundum is fully developed, and the incomplete partition is
manifested as a foramen at about the midpoint of the septum secundum, this foramen is known
as the foramen ovale. That is, the foramen ovale is roughly formed on day 37 - 42.
On day 39 day 42, the upper portion of the septum primum (attached to the cranial portion of
the atrium) regresses, whereas the lower segment (attached to the endocardial cushions)
remains, serving as a flap valve for the formen ovale. At the same time, the edge of the septum
secundum forms the rim of the foramen ovale. That is by about day 39 day 42, intra-atrial
septation is completed.
Conotruncal Septation/Outflow Tract Seperation (Septation Begins: day 29 - 34, Septation Completes:
day 43 49; Separation Begins: day 42 - 44, Separation Completes: day 49 - 55)
Septation of the truncus arteriosus begins around day 29 to day 34 and is completed around day 43 to
day 49. Aorta and pulmonary artery starts to separate from each other around day 42 to day 44. By day
49 to day 52, aorta/pulmonary artery separation is completed.
Ventricular Septation (Muscular Begins: day 28 - 30, Muscular Halts: day 42 44; Membranous Begins:
day 44, Membranous Completes: day 49 52)
Muscular interventricular septum begins to form on day 28. The growth of the muscular interventricular
septum is halted on around day 42 44 (leaving open an interventricular foramen that allows
communication between the ventricles) to wait for the septation of the outflow track. By day 49 52,
membranous part of the interventricular septum is completed (that is, the membranous interventricular
septum fuses with the muscular interventricular septum). That is, closure of the interventricular foramen
occurs around day 49 52.
Formation of Cardiac Valves (Begins: day 34 37, Completes: day 50 - 56)
Hepatic Development + Development of Vitelline Veins & Umbilical Veins (Begins: day 26, Completes:
day 52 56)
On day 26 27, hepatic diverticulum grows into the septum transversum. Shortly thereafter, cells
begin to interact through mutual induction.
On day 28, hepatic diverticulum begins to send out hepatic cords to invade septum transversum.
As soon as hepatic cords invade the septum transversum, hepatic sinusoids begins to appear as
well as the left and right vitelline plexuses, around day 28 29.
On day 29 30, the left and right vitelline plexuses have been incorporated with the hepatic
sinusoids. That is, the vitelline plexus around the liver has become connected to the hepatic
sinusoids.
On day 30 31, the umbilical veins have been linked to the hepatic sinusoids. That is, as the liver
expands, vascular connections between the umbilical veins and the hepatic sinusoids are
established.
On day 32 33, proximal part of both left and right umbilical veins begins to degenerate.
On day 34 35, distal right umbilical vein begins to degenerate.
On day 35, left horn of sinus venosus begins to decrease in size. At the same time (on day 35),
proximal left vitelline vein begins to degenerate and proximal right vitelline vein begins to enlarge
in size.
Also on day 35, distal vitelline veins (left and right) begins modification (and will later form the
portal vein).
On day 35 36, ductus venosus begins to develop (and can now be distinguished).
On day 36, proximal parts of both left and right umbilical veins have now degenerated.
On day 36 40, the hepatic portion of the inferior vena cava develops from the vitelline veins.
On day 38 42, hepatic portal vein has now been formed from the distal vitelline veins.
On day 44, distal right umbilical vein has lost its connection to the hepatic sinusoids. Note that
some remnants still persist at this stage.
On day 49, distal right umbilical vein has now fully degenerated.
Also, on day 49, left proximal vitelline vein has degenerated.
On day 52 56, the left sinus horn has become the coronary sinus.
On day 52 56, the ductus venosus is completely formed.
Note: The third, fourth and sixth aortic arches are welldeveloped by day 35-36.
Development Of Other Gastrointestinal Organs
Gall Bladder and Cystic Duct:
On day 26, cystic diverticulum appears (this begins the development of the gallbladder and cystic
duct).
Pancreas:
On day 26, a dorsal pancreatic bud appears in the dorsal wall of the foregut, opposite to the site
of origin of the hepatic diverticulum.
On day 28, a ventral pancreatic bud appears from the developing bile duct (caudal to the
developing gallbladder.
On day 35, the ventral pancreatic bud has now migrated posteriorly.
On day 42, the ventral and dorsal pancreatic buds fuse.
Spleen: The spleen develops as a condensation of mesenchyme of the dorsal mesentery of the stomach
during the 5th week. That is, the spleen develops from mesenchymal cells between the layers of the
dorsal mesentery (behind the stomach).
Upper Respiratory Tract: On day 22, the upper respiratory tract arises from bony structures of the head.
Lower Respiratory Tract:
On day 22-23, a ventral outpouching is formed from the ventral surface of the foregut, this ventral
outpouching is called laryngotracheal groove (aka respiratory diverticulum).
Shortly after the laryngotracheal groove is formed, the proximal part of the laryngotracheal groove
develops into larynx and trachea.
1. Embryonic Stage (Begins: Day 24; Ends: End of week 7)
Airway Branching: Forming sequential endodermal buds carry with them coast of
mesenchyme.
o Distally, the laryngotracheal groove grows and develops to become the primitive
lung bud on day 24-28. The formation of the lung bud marks the beginning of the
embryonic phase of lung development.
o The primitive lung bud has bifucrcated laterally to form right and left primary
bronchial buds on day 26-30.
o The left and right primary bronchial buds branches asymmetrically, forming lobar
bronchial buds (aka secondary bronchial buds) with three right and two left on
day 31-36.
o Continued branching yield segmental bronchial buds (aka tertiary bronchial
buds) on day 41-42.
o On day 48-49, subsegmental bronchial buds have been formed. The development
of subsegmental bronchial buds marks the end of the embryonic stage and the
beginning of the pseudoglandular stage.
Diaphragm
o Development of the diaphragm which began with the formation of septum
transversum (in the third week), is fully complete on day 49-52.
Pulmonary Vasculature
o On day 24-26, splanchnic plexus arises around the foregut by proliferation of
angioblastic cells probably from the dorsal aortas, ventral aortas, cardinal venous
system, umbilical venous system and sinus venosus.
Recall that on day 26, the lung bud arise as an outgrowth of the primitive foregut
and is thus surrounded by the splanchnic plexus. The part of the splanchnic
plexus in the region surrounding the lung bud can be called the pulmonary
plexus. Therefore, there is already blood circulation to and from the lung
(through the primitive connections of the splanchnic plexus) and connection with
the rest of the embryonic circulation from the earliest point of lung development.
That is, we can say pulmonary vasculature is part of the embryonic circulation
from the moment the lung starts to develop.
On day 29-32, the common pulmonary vein (from the back of the left atrium)
engages and connects with the pulmonary plexus. Shortly after, four individual
pulmonary veins develops (by coalesce) from the pulmonary plexus and are
joined to the common pulmonary vein. Also, the pulmonary plexus gradually
loses its connection with the splanchnic plexus.
On day 38-40, the connections between the pulmonary plexus and the splanchnic
plexus involute.
As the left atrium grows, the transient common pulmonary vein will gradually be
incorporated into the wall of the left atrium, forming the smooth part of the left
atrium, so that the common pulmonary vein no longer exists as an anatomical
structure and the individual pulmonary veins become connected separately and
directly to the left atrium. In more detail, by the end of week 5, there are
openings of two pulmonary veins into the left atrium. And in week 8, there are
four openings.
The proximal left and right pulmonary arteries can be seen to start arise from the sixth
aortic arch on day 32-33. Note: the distal parts of the left and right pulmonary arteries
(and other pulmonary vessels) arise from distal angiogenesis and remodelling of the
pulmonary plexus.
By day 44 - 50, the pulmonary arteries have joined the pulmonary plexus that surrounds
and infiltrates the lung buds.
Pulmonary Vasculature: Recall that the development of the intrapulmonary vessels occur
at all stages and directly corresponds to the overall lung growth. Pulmonary vessels
develop in parallel to the development of the conducting airways of the lung and follow
the same branching pattern. The vascular growth is in close proximity to the conducting
airways. That is, generations of vessels develop alongside sequential generations of
branching airways. All preacinar pulmonary arteries and veins are formed by the end of
the pseudoglandular stage.
Differentiation of the mesenchyme and epithelial (beginning in the more proximal
regions of the airway and progress distally):
Mesenchyme surrounding the branching buds begin to differentiate into blood
vessels, lymphatics, cartilage (chondrocytes), smooth muscles (myofibroblast),
connective tissue (fibroblast) around the epithelial tubes.
Smooth muscles begins to appear at the end of week 7. It is fully
developed during the canalicular stage.
Lymphatics first appear in the hilar region of the lung in week 8 and in the
lung itself by week 10. It is fully developed during the canalicular stage.
Cartilage formation (appearing as ringed cartilaginous exoskeleton)
begins in the proximal airways (trachea & main bronchi) on week 10-11
and continues to move distally forward from that time forward until it
reaches completion. On week 16, cartilage appears in the segmental
bronchi. On week 24-25, cartilage formation is completed where cartilage
has extended to the most distal bronchi (about 10 14 airway
generations).
Epithelial differentiation with the appearance of basal cells, goblet cells,
pulmonary neuroendocrine cells, ciliated cells and nonciliated columnar (Clara)
cells. Most importantly, we will look at the times in which the epithelial cells
differentiate into ciliated cells and goblet cells and submucosal glands.
Isolated neuroepithelial cells appear in proximal airways in week 8-9. By
week 9-10, they have formed clusters.
Basal cells in the large airways appear as early as week 10.
Cilia begins to appear in week 10 in the trachea & extends to the main
stem bronchi in week 12. In week 13, cilia are found in the segmental
bronchi.
Goblet cells begins to appear in the epithelium at week 13-14. Note that
goblet cells produce airway mucus. Goblet cells extends to the most
proximal intrasegmental bronchi by week 24. With increasing gestational
age they extend distally down to the bronchioles.
Submucosal gland begins to appear at week 13-15. On week 24-25,
submucosal glands have extended as far down the airway as they do in
the adult lung.
Clara cells in the bronchioles appear as early as week 16-17. These clara
cells initially exhibits large glycogen stores (immature Clara cells). Later
the glycogen stores are replaced by secretory granules forming mature
Clara cells on week 19.
pneumocytes begins around week 22 24. The epithelium is thin enough to allow for
some gas exchange by week 24 25. Sufficient quantities of surfactants are produced by
week 24 26 for some gas exchange to take place.
Note: By the end of the canalicular stage, survival of the fetus becomes possible. Some
authors even suggest around week 22 24. The respiratory system (the air-blood barrier)
at the end of the canalicular stage have the capacity to perform some gas exchange. That
is, some respiration may be possible towards the end of this stage. However premature
infants born at this stage still have quite poor prognosis. Exogenous surfactant and
respiratory support are frequently needed.
true alveoli until after birth, at which time they are only
shallow bulges of the walls of the terminal sacs and
respiratory bronchioles.
During the saccular stage, there are further compression of the intervening interstitium
(that is mesenchyme continues to thin) and thinning of the epithelium. There is a marked
decrease in the prominence of the interstitial tissue and a marked thinning of the
airspace walls.
5. Alveolar Stage
The alveolar stage of lung development extends from approximately week 32 - 36 until 18
postnatal month, but most alveolarization occurs within 5-6 months following delivery at term.
During the alveolar stage, alveolarization continues. Saccules develop into alveolar ducts or
alveolar sacs with numerous alveoli.
APPENDIX
Carnegie Stage
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Day
1
23
45
67
8 12
13 14
15 17
17 19
19 21
22 23
24 25
26 28
29 30
31 35
35 38
37 42
42 44
44 48
48 51
51 53
53 54
54 56
56 60
Somites
17
7 13
13 20
20 29
29 35
35 44
> 44 (?)
?
?
?
?
?
?
?
?
Length
0.1 0.15mm
0.1 0.2mm
0.1 0.2mm
0.1 0.2mm
0.1 0.2mm
0.2mm
0.4mm
1 1.5mm
1.5 2.0mm
2.0 2.5mm
2.5 3.0mm
3.0 4.0mm
4.0 5.0mm
5.0 7.0mm
7.0 9.0mm
8.0 11mm
11 14mm
13 17mm
16 18mm
18 22mm
22 24mm
23 28mm
27 31mm