Chapter 2:   Development of the Choroid Plexus


Amniotic fluid is present initially in the primitive cerebral recesses of the human embryo, but then the ependymal cells and eventually the growing choroid plexuses take over the production of cerebrospinal fluid118.  A series of experiments on dogs performed by Walter Dandy in Baltimore in 1911 confirmed that the  production of cerebrospinal fluid was a function of the choroid plexus. The ventricles begin their growth when the caudal neuropore closes at about 28 days118,143.   At this time the ventricular system becomes isolated from the amniotic cavity.  It is supposed that normal brain enlargement and formation, to a certain extent, relies on the pressure applied from within by the ventricular fluid, just as the eventual shape of the ventricular cavities is determined by the growth and structure of the surrounding brain tissues143. 


In the normal adult about 500mls of CSF is produced daily240.  The function of CSF is not fully understood, although it is considered mainly to be a shock-absorber, it contains many nutrients, particularly in embryonic and fetal development, and may be a carrier of neuro-transmitting molecules. 

2.1           Choroid Plexus Growth & Development

Choroid plexus (from the Latin chorion  = coat, and plectere = to plait or braid) tissue is found in the third, fourth and both lateral ventricles of the human brain.  The choroid plexuses are developmentally fetal structures, forming at the end of the embryonic period.  The growth of the choroid plexus in the ventricular system begins in the third ventricle, on the roof of which the choroidal plate forms.  In the lateral ventricles, the first signs of an invagination of vascular mesenchyme (connective tissue derived from the mesoderm germ layer) into the roof of the ventricle occur at six to seven weeks (CRL = 17 - 19 mm).   Anteriorly, this invagination (the area epithilealis) is in contact with the choroidal plate of the third ventricle (the paraphyseal arch) and it passes posteriorly and superiorly along a curved area of indentation in the medial ventricular wall called the choroidal fissure.  Uniquely, in this region the pia mater is in direct contact with the ependymal cells of the ventricle.  Special cells, the choroid villi, begin to appear on the plexus at around stages 20 and 21 (seven weeks) as the process of differentiation of the choroid plexus from the fissure continues with a finger-like process into the ventricle that moves around the fissure towards the pes hippocampus in the temporal horn, where it terminates196


Several stages of developing complexity in the structural appearance of the lateral ventricular plexus were described by Shuangshoti and Netsky173, based on cross-sections of embryonal and fetal brains. 

2.2           Stage I

 At 7 - 9 weeks, the choroid plexus of the lateral ventricles begins as a club-shaped structure with a short stalk, as shown in Fig 1.  The stroma (supportive structure) of the plexus is loosely organised mesenchyme.  The shape of this club becomes more lobulated towards the end of this period. 


Fig 1.  Section of fetal brain, showing the choroid plexus during Stage 1. (From Shuangshoti and Netski173.) 



O’Rahilly and Müller143 describe how some of the newly forming villi near the base of the plexus at this stage are “slender and vesicular.”

2.3           Stage II

(9 -17 weeks), the plexus is extremely large in relation to the size of the ventricle, occupying about one third of its volume.  Glycogen appears abundantly in the cytoplasm of the endothelial cells.   The stromal mesenchyme is extremely loose, and secretes large amounts of mucin, a sticky substance.  The lobulations are becoming more and more pronounced, as demonstrated in Fig 2.  As a result, towards the end of this period and into the next stage, many tubules are formed within the lobulated plexus when the mesenchyme folds onto itself, creating blind tracts that are usually filled with CSF.  Completely entrapped areas distend to form cysts, which grow with CSF production to variable sizes.  According to Shuangshoti and Netski: 


 ... the tubules we find are formed by the folding of the surface epithelium into the stroma during differentiation of the plexus The number of tubules increase at the same rate as the number of lobules or villi of the plexus, indicating that formation is closely related to the inter-lobular or inter-villous clefts.  These tubules are formed when the tips of these clefts are pinched off.  We find these tubules in all three major plexuses.  Tubules in seven specimens are large enough to be designated as incipient neuroepithelial cysts.173 



Fig 2. Section of fetal brain in early Stage II showing increasing lobulation of the choroid plexus. (From Shuangshoti and Netski173. Arrow point to choroid in the roof of the 3rd ventricle.)


2.4           Stage III

 (17 - 29 weeks), the relative size of the plexus is reducing but the lobulation continues to become more complex, as demonstrated in Fig 3.  Glycogen is less abundant in the cytoplasm.  During this stage, the amount of loose stroma decreases as connective tissue fibres increase.  Large numbers of small tubules are present, but towards the end of this stage the cysts disappear as the relative amount of mucin decreases.  Fluid is released when the mesenchymal elements become unstuck, perhaps with the assistance of pressure from within the cyst. 




Fig 3.  Section of choroid plexus showing complex lobulation and the intervillous spaces. (From Shuangshoti and Netski173.)


2.5           Stage IV

At this stage (29 weeks on), the villi are finer and more delicately frond-like.  The plexus is smaller compared to the ventricle.  Many small tubules persist, and the mesenchymal elements become scant as connective tissue fibres predominate.  Almost all cysts are gone.

2.6           Conclusion

The increasingly complex structure of the choroid plexus during its growth in the second trimester with the development of many tubules into incipient cysts, provides an explanation for the origin of CPC in the brain of both normal and trisomic fetuses.  The change in mucin production and the gradual reduction in larger tubules appears to explain the gradual resolution of these cysts.