FOLDING OF THE EMBRYO In this lecture we

FOLDING OF THE EMBRYO

• In this lecture we shall concentrate on those events which transform the trilaminar embryo into a • “tube within a tube”, segregating the embryo from extraembryonic tissue except at the umbilicus.

• These processes will also rotate the developing heart tube into its thoracic position. • Finally, we shall examine how the coelom is divided into the pleural, peritoneal and pericardial cavities.

Learning objectives • 1. To understand how the embryo is segregated from the extra-embryonic tissues with the exception of the umbilical cord. • 2. To understand the process whereby the gut tube is formed and is lined with endoderm.

• 3. To understand the events that result in the incorporation of the extra-embryonic coelom into the embryo, thereby forming the peritoneal, pericardial and pleural cavities.

• 4. To understand the role of cranial-caudal flexion in the repositioning of the buccopharyngeal membrane (future opening of the mouth), heart tubes, primitive pericardial cavity and a wedge of mesoderm (septum transversum) which will initiate diaphragm formation.

• At the same time the cloacal membrane (future opening of gut and urinary tract) is also brought into a ventral position. • 5. To understand how the diaphragm is formed.

• At the end of the third week, the germ disc begins to overgrow the yolk sac, ballooning into a convex shape, with the peripheral areas of the germ disc becoming the ventral surface of the embryo.

• During 4 th week a significant event in the establishment of body-form is folding. • Folding converts flat trilaminar embryonic disc into a cylindrical embryo.

• Folding occurs in both longitudinal and transverse planes. • The longitudinal and transverse foldings occur simultaneously.

• Concurrently, there is relative constriction at the junction of embryo and yolk sac. • Folding is due to rapid growth of central nervous system and somites. • The growth rate at the sides of the embryonic disc fails to keep pace with the rate of growth in the long axis as the embryo increases rapidly in length.

• Developing embryo during 4 th week • Longitudinal and Transverse foldings are in process

Longitudinal Folding • Mainly due to rapid growth of neural tube. • Ends of the trilaminar germ disc folds ventrally and produce head and tail folds.

• Beginning of fourth week, neural tube in cranial region grows very rapidly. It thickens to form the primordium of the brain. • As the embryo grows the head region projects over the prochordal plate or buccopharyngeal membrane (future site of stomodeum).

• Folding of the caudal end of the embryo results primarily from the growth of distal part of neural tube – the primordium of spinal cord. • As the embryo grows the tail region projects over the cloacal membrane (future site of the anus).

• Initially, (day 18) the developing brain projects dorsally into the amniotic cavity. • Prochordal plate is anterior to the developing neural tube and cloacal plate is posterior to the neural tube. • The connecting stalk along with allantois is posterior to cloacal membrane. • Developing heart tube is inferior to pericardial cavity. • Septum transversum is anterior to pericardial cavity.

• Later (day 22) the developing forebrain grows cranially beyond buccopharyngeal membrane and overhangs developing heart. • Concomitantly, the septum transversum (transverse mesodermal septum), primordial heart, pericardial cavity, and buccopharyngeal or oropharyngeal membrane move onto ventral surface of the embryo. • A small foregut and hindgut has developed.

• Buccopharyngeal membrane is vertical (ectoderm is anterior, endoderm is posterior). Pericardial cavity is now inferior to heart tube. Septum transversum is posterior to heart tube and pericardial cavity. • Cloacal membrane is vertical. Connecting stalk and allantois has gone inferior to hindgut but they are directed posteriorly.

• Day 25. Now the buccopharyngeal/oropharyngeal membrane and cloacal membrane have completed 180 degree turns (ectoderm is inferior and endoderm is superior). Note that the rotation is more in tail fold than head fold. • Foregut and hindgut have elongated. • The connecting stalk and allantois are now directed (project) inferiorly/ventrally. • The constriction of yolk sac is now obvious.

• Day 28. Oropharyngeal and cloacal membranes have rotated more and now facing each other. • The yolk sac has further constricted. Midgut is now clear but still connected to yolk sac through narrow canal called vitelline duct. • Connecting stalk along with allantois has gone nearer to vitelline duct and associated splanchnic mesoderm.

• During longitudinal folding, part of the endoderm of the yolk sac is incorporated into the embryo as the foregut and hindgut. • The foregut lies between the brain and heart. Oropharyngeal membrane separates the foregut from the stomodeum.

The terminal part of the hindgut soon dilates slightly to form cloaca (primordium of urinary bladder & rectum).

• After folding, the septum transversum lies caudal to the heart where it subsequently develops into the central tendon of the diaphragm. • Before folding, the primitive streak lies cranial to the cloacal membrane; after folding, it lies caudal to it.

• After folding the connecting stalk and the vitelline duct join each other and finally form umbilical cord.

• The folding also affects the arrangement of the embryonic coelom (primordium of body cavities). • Before folding, the coelom is a flattened, horseshoeshaped single continuous cavity.

• After folding, the coelom has become divided into thoracic and abdominal cavity. • Thoracic (pericardial) and abdominal (peritoneal) cavities communicate each other through pleuropericardial canals.

Transverse Folding • The flat germinal disc also folds in horizontal or transverse direction. • Right and left lateral edges of trilaminar germ disc not only grow laterally but also move ventrally and finally medially to meet in the midline. • As the lateral edges of embryonic disc grow they form right and left lateral folds.

• Right and left lateral edges of trilaminar germ disc grow • laterally • ventrally and • finally medially to meet in the midline • lateral edges form right and left lateral folds.

• Transverse folding is produced by the rapidly growing somites and neural tube. • The primordium of the ventrolateral wall grows laterally, ventrally and medially towards the median plane, rolling the edges of the embryonic disc and forming a roughly cylindrical embryo.

• By the middle of 3 rd week (day 17) a flat trilaminar germinal disc has formed.

• Development of paraxial mesoderm and formation of somites is mainly responsible for transverse folding of embryo. • As the paraxial mesoderm starts developing the ectoderm is raised bilaterally and neural groove forms between these bilateral ridges. • Paraxial mesoderm later forms somites. The formation of somites and neural tube further raises surface ectoderm dorsally.

• By the day-19 paraxial mesoderm has formed. The neural groove is visible. The ectoderm shows bilateral ridges. In the lateral plate of mesoderm small spaces have started developing.

• Day-20. Somites have started forming. They are thickening and raising folds of developing neural tube. • Lateral plate mesoderm has become divided into somatic and splanchnic mesoderms. Intra-embryonic coelom has formed. It is communicating with extraembryonic coelom.

• Day-21. intra-embryonic coelom is well developed now. The somites are more thickened. The embryo is assuming a globular form.

• Day-22. Somites have further enlarged. Neural tube has formed. Intra-embryonic coelom is wide. The yolk sac is decreasing in size. Embryo is more globular in shape.

Day-25. The blue amnion is almost surrounding the developing embryo. The yellow yolk sac is constricted and going to be divided into intra-embryonic and extra-embryonic parts. Initially, there is a wide connection between the midgut and yolk sac but after lateral folding the connection is reduced to a yolk stalk. Intra-embryonic coelom and extra-embryonic coeloms still communicating.

• Day-28. The right and left growing edges of amnion have merged with each other. The right and left edges of surface ectoderm and parietal mesoderm have joined each other. Intra-embryonic coelom is now within the body of embryo.

• As the abdominal walls form, part of the endoderm germ layer is incorporated into the embryo as the midgut. Midgut is suspended to the dorsal body wall by dorsal mesentery.

• As a result of longitudinal and transverse folding the area of attachment of the amnion to the ventral surface of the embryo is reduced to a relatively narrow umbilical region. Connecting stalk and vitelline duct join and form umbilical cord. The amnion surrounds the umbilical cord from all sides.

• As the lateral folds and longitudinal folds fuse ventrally and umbilical cord forms, the communication between the intraembryonic and extraembryonic coelomic cavities is reduced. • As the amniotic cavity expands it obliterates most of the extraembryonic coelom. • The amnion forms the epithelial covering of the umbilical cord. • Body folding abnormalities are uncommon.

Fourth Week • Major changes in body form occur during the fourth week. • At the beginning, the embryo (2. 0 to 3. 5 mm long) is almost straight and has 9 pairs of somites that produce conspicuous surface elevations.

• The neural tube is formed between right and left chains of somites. • Pharyngeal (branchial) arches are visible. • The embryo is now slightly curved because of the head and tail folds. • The heart produces a large ventral prominence and pumps blood.

Fourth Week

• Forebrain produces a prominent elevation of head, and folding of embryo has given embryo characteristic C-shaped curvature. A long, curved tail is present. • Upper limb buds become recognizable by day 26 or 27 as small swellings on the ventrolateral body walls. • Otic pits, primordial of internal ears, are also visible. • Lens placodes are visible on the sides of the head.

• The fourth pair of pharyngeal arches and the lower limb buds are visible by the end of the fourth week. • End of fourth week, an attenuated tail is a characteristic feature. • Rudiments of many of the organ systems, especially the cardiovascular system, are established. • End of fourth week caudal neuropore is closed.