During the formation of the neural tube and ectomesenchyme, things are far from static in the other germ layers. To appreciate what else has been going on, we need to step back a few days.
By the middle of the third week, the embryo consists of three layers of cells. The ectoderm is continuous with the wall of the amnion above, the endoderm with the wall of the yolk sac below. The mesoderm is continuous with the extraembryonic mesoderm peripherally and sepa- rates the ectoderm and endoderm, except along the midline where it
Fig. 8.4 Neurulation and formation of ectomesenchyme.
A B
C D
Neural crest Ectoderm
Notochord
Neural plate Neural groove
Ectomesenchyme
Migrating ectomesenchyme
Spinal ganglion
Neural tube
The fi rst three weeks of development 57
is interrupted by the notochord centrally, the buccopharyngeal mem- brane, and cloacal membrane as described on p. 55 . The neural tube is forming and ectomesenchyme is shortly to be added to the three extant germ layers. The ultimate fate of the cells emanating from each germ layer has already been indicated in general terms , but we need to exam- ine some aspects of the further development of the germ layers, particu- larly the mesoderm, to appreciate how they give rise to more specifi c derivatives.
Mesoderm
The intraembryonic mesoderm initially forms a thin sheet of tissue on either side of the midline as it migrates from the overlying ectoderm. By day 17, the mesoderm on either side of the notochord proliferates and thickens to form a mass of tissue, the paraxial mesoderm. The meso- derm lateral to the paraxial mesoderm is the intermediate mesoderm and lateral plate mesoderm occupies the most lateral area.
The destination and subsequent fate of mesodermal cells is deter- mined by their migration route through the primitive streak and node.
The fi rst formed intraembryonic mesoderm migrates through the most caudal part of the primitive streak and becomes lateral plate mesoderm.
Cells migrating through the same area a little later become intermediate mesoderm. Epiblastic cells passing through near to the primitive node and in the superior areas of the streak become paraxial mesoderm.
The light green arrows in Figure 8.3B show how some of the mesoderm migrates superiorly to extend around the buccopharyngeal membrane.
This area of mesoderm is known as cardiogenic mesoderm and is the site where heart development begins.
The formation of somites from paraxial mesoderm
By the end of the third week of development, the paraxial mesoderm has proliferated to form two solid rods of tissue, one on each side of the central notochord. Follow up the mesoderm from the inferior end of the embryo in Figure 8.5A ; about one-third of the way superiorly, you can see whorls of cells called somitomeres appearing at intervals along the paraxial meso- derm. In reality, somitomeres fi rst appear adjacent to the superior end of the notochord. As shown in Figure 8.5A , the cell whorls clump together, a process known as condensation, to form bilaterally paired cuboidal masses, the somites, either side of the notochord and developing neural tube ; the condensing somites are clearly visible as bilateral lumps at the superior end of the embryo under the overlying ectoderm. This process is referred to as segmentation and recapitulates the repeated segmental body pattern of our remote evolutionary ancestors outlined in Box 3.3 .
Segmentation progresses from head to tail and the number of pairs of somites is often used as a measure of the age of the embryo. By the end of the fi fth week of development, there are 42–45 pairs of somites. These are classifi ed according to the areas of the body they give rise to into four occipital (or metotic), eight cervical , 12 thoracic , fi ve lumbar , fi ve sac- ral , and 8–10 coccygeal somites. You may realize that the numbers of cer- vical, thoracic, lumbar, and sacral spinal nerves are identical to the number of somites in the same area (see Section 3.3 ); this is no coincidence, but another manifestation of the same basic segmental patterning. The ‘extra’
somites in this scheme are the four pairs of occipital somites that eventual- ly contribute tissue to the skull and tongue (see Section 21.6 ) and the coc- cygeal somites, the majority of which disappear as development proceeds.
Peripheral nerve development is related to somite development. There appears to be no overt segmentation of the spinal cord and motor nerves grow out from the developing spinal cord as a continuous set of rootlets.
Sensory ganglia are formed from condensations of ectomesenchyme as it migrates laterally from its position above the neural tube. The migration route of the neural tissue is constrained by the somites; the superior part of each somite allows nerves to pass through but the inferior part inhibits their passage. The nerves are, therefore, channelled along specifi c routes to form distinct spinal nerves related to the superior end of each somite.
The motor nerves aggregate with the peripheral components of the sen- sory nerves to form mixed spinal nerves beyond the ganglia.
Further diff erentiation of somites
As segmentation progresses from head to tail, the fi rst formed somites begin to diff erentiate further during the fourth week of develop- ment. As can be seen in Figure 8.5B , each somite has a vertical, slit- like cavity, the myocoel, which is soon obliterated by cell division as the somite grows. The tissue lateral to the myocoel is the dermatome
Superior (head)
Buccopharyngeal membrane
Inferior (tail)
Somites
Somitomeres
Paraxial mesoderm Notochord A
Dermatome Myocoel Myotome Sclerotome
Neural tube
Notochord B
Fig. 8.5 Diff erentiation of somites. A) Somite formation seen from above; B) Somite formation in cross section.
58 Embryonic development—the fi rst few weeks
and will eventually spread out beneath the ectoderm to become the dermis of the skin. The somite tissue medial to the myocoel has two divi- sions. The medial division nearest the notochord is the sclerotome; this diff erentiates into connective tissue or mesenchyme and migrates to form a mass of tissue around the notochord and developing neural tube.
The mesenchyme derived from the sclerotome will eventually form the vertebral column, ribs, and sternum. The lateral division becomes the myotome which diff erentiates into muscles of the vertebral column, the intercostal muscles between the ribs, and the limb muscles in the lower cervical and upper thoracic region, and lumbar and sacral regions.
The intermediate mesoderm lateral to the developing somites gives rise to the urinary system, the adrenal cortex, and much of the repro- ductive system. The lateral mesoderm of the intraembryonic meso- derm is continuous with the extraembryonic mesoderm surrounding the amniotic cavity and yolk sac; its further development involves the formation of a new cavity, the intraembryonic coelom.
The somites are confi ned to the region of the embryo between the buccopharyngeal and cloacal membranes. However, as seen in Figure 8.3B , lateral plate mesoderm extends into the areas anterior and pos- terior to these two membranes. A series of vacuoles appear in the lat- eral plate mesoderm and coalesce to form the intraembryonic coelom.
As shown by the pink-shaded area in Figure 8.6 , the intraembryonic coelom develops into a U-shaped cavity with its base in front of the buccopharyngeal membrane, linking its two arms that pass backwards each side of the paraxial mesoderm. The anterior part of the intraem- bryonic coelom is the primitive pericardial cavity where cardiogenic mesoderm will form the heart and the lateral limbs are the primitive pleural and peritoneal cavities that enclose the lungs and abdominal viscera, respectively. Lateral to the arms of the U, the mesoderm breaks down so that intraembryonic and extraembryonic coeloms are con- tinuous over a certain distance. These cavities act as a primitive circula- tory system to distribute fl uids and their nutrients around and into the embryo (see Section 13.2.1 ). Eventually, these cavities will be replaced by true blood vessels.
Fig. 8.6 Formation of the intraembryonic coelom.
Buccopharyngeal membrane
Somatic layer of mesoderm Communication between coeloms Visceral layer of mesoderm
Intraembryonic coelom
Extra-embryonic coelom Endoderm Mesoderm Neural plate
Box 8.3 Embryonic stem cells
Blastomeres are totipotential stem cells that can form a whole embryo. As the germ layers form, the potential fate of the cells becomes more restricted to form certain types of cell; the repertoire of cells that can develop from a given set of embry- onic cells become more restricted as development proceeds.
The most obvious example of progressive restriction is when the paraxial mesoderm segregates into dermatome, myotome, and sclerotome. Myotome cells can only become muscle cells whereas sclerotome cells can give rise to cells that will form bone, cartilage, and other elements of the skeletal system.
In most tissues and organs, some cells remain in an embryonic state as stem cells and can give rise to new cells to replace cells damaged by disease, trauma, or general wear and tear. The cells forming the basal layer of skin epithelium are a good example of ‘permanent’ stem cells; as cells are lost from the surface of the skin in the course of daily activities, they are replaced from below. A basal cell will divide and one of the daughter cells will mature into a skin cell whereas the other cell will remain in the basal layer as a stem cell to divide again and again as circum- stances demand.
One of the objectives of developmental biology research is to be able to identify and isolate these undiff erentiated stem cells from diff erent tissues. By manipulation of these cells in the laboratory by providing the correct nutrients and appropriate signalling molecules, the stem cells can be directed down a specifi c line of diff erentiation to produce new cells. The new population of cells could then be reintroduced into the body to replace cells lost through trauma and disease. Although progress in this fi eld is rapid, we are still a long way from being able to use this technol- ogy as a cure for various diseases.
Folding of the embryonic plate and its consequences 59
Buccopharyngeal membrane
Buccopharyngeal membrane ruptured
Cloacal membrane
Developing heart
A B
C D
Foregut
Midgut
Hindgut
Vitelline duct Lateral plate mesoderm
in future septum transversum Ectoderm
Endoderm
Neural plate
Yolk sac
Notochord Primitive
pericardial cavity
Fig. 8.7 Longitudinal folding of the embryo.
As already indicated, the endoderm forms the cells that line the respira- tory and gastrointestinal tracts. The fl at embryonic disc has to become folded if the endoderm is going to be in a suitable location to become these linings.
In earlier stages of development, the embryo is a fl at plate of cells diff erentiating into the diff erent germ layers. The growth of the ecto- derm during formation of the neural tube and of mesoderm during segmentation has been described; this growth has profound con- sequences for the relative positions of the embryonic germ layers and specifi c structures formed from them. Most of the growth takes place on the dorsal surface initially and the principal eff ect is that the embryo bulges upwards into the amniotic cavity. The resulting fold- ing or fl exion of the embryo is not confi ned to the transverse axis but occurs longitudinally too.
We will follow a series of diagrams illustrating the folding of the embryo in longitudinal and transverse sections to observe the con- sequences of folding on the relative position of diff erent organs and tissues.