Evolution of the Mesoblast: Preview

Compiled by UTCOM Class of 2013 Block 2 Unit 1

Evolution of the Mesoblast

Terminology: Extraembryonic is formed already during the 2nd week; is involved in the construction Mesoblast of the placenta and the other appendage organs. Intraembryonic the third germinal layer; arises in the 3rd week via the immigration of Mesoblast cells at the primitive streak; out of this develop the various tissues and organs of the embryo.

In the beginning, the cells of the mesoblast (mesodermal cells) build a thin, widely meshed layer on both sides of the median line, between the ectoderm and the endoderm. While the notochord is forming—it grows to the same extent that the primitive streak recedes—the intraembryonic mesoderm cells multiply on both sides of the median line and so form 3 structures in the shape of longitudinal columns: the paraxial mesoderm, the intermediate mesoderm, and the lateral plate mesoderm. This process begins at the cranial pole and continues up to the 4th week in the caudal direction [see pictures below].

Mesoderm After the Completed Mesoblast Immigration: Day 25 Evolution of Mesoblast: Day 25

1 Paraxial mesoderm 2 Intermediate mesoderm 3 Lateral plate mesoderm 4 Neural groove 5 Ectoblast 6 Endoblast

Simple Rendering 1 Paraxial mesoderm 7 Endoblast 2 Intermediate mesoderm 8 Ectoblast 3 Lateral plate mesoderm 9 Somatopleural (mesoderm, ectoderm) Detailed Rendering 4 Chordal process 10 Splanchnopleural (mesoderm, endoderm) 5 Intraembryonic coelom 11 Neural groove 6 Amnion 12 Neural plat

Not authorized to be reproduced or distributed for commercial purposes of any kind. 24 Compiled by UTCOM Class of 2013 Block 2 Unit 1

Paraxial Mesoblast Terminology: Somitomeres indistinct aggregates of paraxial mesoderm along embryo’s rostral-caudal axis; adjacent to neural tube. Somites segmented; 1-7 form the striated muscles of the face, jaws, and throat; more caudal somites give rise to sclerotome, myotome, & dermatome. Pharyngeal Arches derived from somites 1-7; contribute to development of head and neck. Sclerotome somite precursor of vertebral column. Myotome somite precursor of striated muscle of neck, trunk, and limbs. Dermatome somite precursor of subcutaneous tissue and skin.

The paraxial mesoblast comes from the epiblast Intraembryonic Coelom: Day 23 cells that migrated into the region of the primitive node (or the cranial portion of the primitive streak). It forms a pair of cylindrical, epithelially-organized mesenchymal segments that are in the immediate vicinity of the neural tube and the notochord. After the start of the 3rd week, these cylinders become segmented from the cranial to the caudal end into somitomeres [see pictures to right]. Except for the somitomeres (1 to 7) that form no somites—but are involved in the formation of the pharyngeal arch mesoblast—the others form somites in the cranio-caudal direction. The somite pairs are formed along the neural tube and range from the cranial region up 1 Paraxial mesoderm 2 Intermediate mesoderm to the embryo’s tail. In the end, the human embryo will 3 Lateral plate mesoderm have approximately 35-37 somite pairs. The number of 4 Chordal process 5 Sectional edge of amnion somites is used to roughly determine the embryo's age 6 Intraembryonic coelom in this developmental stage. The somites are formed through the Somitomere Appearance: Day 25 segmentation of the paraxial mesoderm. They organize themselves without cell differentiation. They are responsible for the segmental organization of the embryo and contribute to its restructuring. They will develop into three distinct regions: the sclerotome, the myotome, and the dermatome. The segmental partitioning of the spine, the neural tube, the trunk wall and the thorax (ribs) depends on the ordered arrangement of the somites.

Intermediate Mesoblast 7 Endoblast The intermediate mesoblast is found between the 8 Ectoblast 9 Somatopleure with ectoblast paraxial mesoblast and the lateral plate mesoblast. This 10 Splanchopleure with endoblast longitudinal, dorsally lying crest is called the urogenital crest and serves as the origin of the kidney and gonads.

Lateral Plate Mesoblast

Terminology: Intraembryonic represents the future serous cavities of the trunk (i.e., the pleural, Coelom peritoneal, and pericardiac cavities). Somatopleure consists of somatic mesoderm and ectoderm; dorsally located; gives rise to connective tissue and some vascular smooth muscle. Splanchopleure consists of visceral/splanchnic mesoderm and endoderm; ventrally located; gives rise to smooth muscle of the GI tract and cardiac

The lateral plate Lateral Plate Mesoderm: Day 23 Lateral Plate Mesoderm: Day 25 mesoderm is composed of two thick layers that surround a cavity, called the intraembryonic coelom (the coelom represents the future serous cavity of the trunk: peritoneal, pleural and pericardial cavities). The somatopleure, which is close to the ectoderm, is involved in the formation of the lateral and ventral 1 Lateral plate mesoderm 8 Notochord walls of the embryo. The 2 Intermediate mesoderm 9 Splanchopleure with splanchnopleure, which 3 Paraxial mesoderm endoderm 4 Neural groove 10 Somatopleure with ectoderm lies on the endoblast, takes 5 Coelomic vacuoles 11 Amniotic cavity part in the formation of the 6 Intraembryonic coelom 12 Umbilical vesicle wall of the digestive tube. 7 Somites

The Intraembryonic Coelom The intraembryonic coelom first appears in the lateral plate mesoderm as the lateral plate mesoderm begins to split into the dorsal somative mesoderm (somatopleure) and the ventral splanchnic mesoderm (splanchnopleure).Initially, it looks like several isolated vacuoles. During the lateral unfolding of the embryo in the 4th week, these vacuoles fuse and form a U-shaped cavity: the intraembryonic coelom. In the beginning, a connection exists between the intra- and extraembryonic coeloms. With the progress of the unfolding, though, the merging of the ectoblast layers along the medial line has the effect that the intraembryonic coelom is separated from the extraembryonic one and remains enclosed in the lateral mesoblast. The intraembryonic coelom will give rise to the futurer serous cavities of the trunk— including the thoracic cavities (i.e., pleural and pericardial) and abdominal cavity (i.e., peritoneal).

Differentiation of the Mesoblast

NOTA BENE: SEE DR. CHIAIA’S LECTURE ON THE “DEVELOPMENT OF THE MUSCULAR SYSTEM” FOR ADDITIONAL INFORMATION.

Induction of the Neural Plate Terminology: Neurulation the formation of the embryonic neural plate and its transformation into the neural tube. Primary Neurulation process in human embryos by which cells of the neural plate invaginate and pinch off to form the neural tube. Neural Plate a flat region of neuroectodermal cells which lies directly above the notochord; the first-formed embryonic rudiment of the CNS; during neurulation, it will become the neural tube. Neural Tube longitudinal tube of neural tissue formed by the rolling up of the neural plate until the neural folds join in the mid-dorsal line and the epidermis fuses above; precursor of the brain and spinal cord. Neural Crest located between the neural tube and epidermis during neural tube formation; migrate immediately after neural tube closure; sometimes referred to as the fourth germ layer. Early in the development of an embryo, a strip of specialized cells called the notochord induces the cells of the ectoderm directly above it to become the primitive nervous system (i.e., neuroectoderm) [A, see diagram]. The appearance of the neural plate represents the first step in the genesis of the nervous system. The neural plate is identifiable as the medio-sagittal thickening of the ectoblast rostral to the primitive streak. At the cranial end, the neural plate is wider and gives rise to the brain. At the caudal end, it is narrower and gives rise to the spinal cord. In the third week, the edges of the neural plate rise up and become neural folds enclosing the neural groove [B, see diagram]. As the tips of the folds fuse together, a hollow tube (i.e., the neural tube) forms [C, see diagram]. The neural tube is the precursor of the brain and spinal cord. Meanwhile, the ectoderm and endoderm continue to curve around and fuse beneath the embryo to create the body cavity— completing the transformation of the embryo from a flattened disk to a three-dimensional body. Cells originating from the fused tips of the neuroectoderm (i.e., neural crest cells) migrate to various locations throughout the embryo, where they will initiate the development of diverse body structures [D, see diagram]. The neural crest cells form, so to speak, a 4th embryonic germinal layer. This contains a partial segmentation that contributes to the formation of the peripheral nervous system (neurons and glia cells of the sympathetic, parasympathetic and sensory nervous systems). The neural crest cells are distinguished by a great migrating ability and phenotypic heterogeneity, since numerous and various differentiated cell types will arise from them: PNS nerve and glia cells; epidermal pigment cells (melanocytes); calcitonin cells of the thyroid gland; cells of the adrenal medulla; some components of skeletal and connective tissue in the head area.

Additional views of the Neural Plate: Day 23 Neural Plate: Day 25 closure of the neural tube:

(follow the arrows in order to trace the process by which the neural tube develops)

1 Neural plate 5 Somites 2 Primitive streak 6 Cut section of amnion 3 Primitive nodes 7 Neural folds 4 Neural groove

Neural Plate and Neural Crest Neural Tube: Day 28

1 Neural tube A Neural plate stage B Neural groove stage 2 Neural fold 1 Epiblast 2 Neural groove 3 Neural groove 3 Neural crest 4 Somites Migrating Neural Crest Neural Tube Neural Tube: Day 29 Cells

1 Epiblast 4 Neuroepithelium 5 Neural crest rotrusion 2 Neural fold 5 Central canal 6 Pericardium p Migrating neural crest cells 7 Cranial neuropore 3 Neural tube 6 8 Caudal neuropore

Folding of the Germinal Disc

Terminology: Pericardium one of three serous cavities which develops in the embryo/fetus. Septum Transversum thick mass of cranial mesenchyme which gives rise to parts of the thoracic diaphragm and the separates the intraembryonic coelom into thoracic and abdominal cavities. Cardiac anlage the initial clustering of embryonic cells that serves as a foundation from which the heart develops Allantois a pre-placental, pre-urinary tract (the placenta later becomes the main organ for the removal of nitrogenous waste products); allantoic blood vessels will become part of the umbilical cord after embryonic folding.

After the third week, the three germinal layers begin to differentiate and transform so that the initially flat embryonic disk develops into a cylindrical structure like a "C". The folding and genesis of the abdominal wall permits a delimitation of the embryo. At this point, the extraembryonic tissue folds over into the intraembryonic tissue with no boundaries. The folding and the resulting formation of the abdominal wall lead to an enclosure of the mesoderm and the endoderm. They become surrounded by the ectoderm, which later forms the skin.

Two mechanisms lead simultaneously to the formation of the abdominal wall [see picture to left]:

. The cephalo-caudal flexion (in the longitudinal direction) takes place in the A plane. . The lateral folding (in the transversal direction, rolling up) takes place in the C plane.

NOTA BENE: For the sake of completeness, a general overview of both the cephalo-caudal folding and the lateral folding has been prepared. On the following pages, a comparison of the two folding patterns has been presented side by side. Examine the sequence of images in a columnar fashion (i.e., read the left-hand column from the top of the page to the bottom of the page before reading the right-hand column in the same fashion; arrows have been provided).

NOTA BENE: Each set of images has a numerical code at the top left corner. The first number indicates the Carnegie stage at which the given embryonic structure appears; the second number indicates the day at which the given embryonic structure appears. Subsequent images in this section will have a similar numerical tag.

The Lateral Folding (transversal direction) At the same time as the cephalo- caudal flexion, a lateral folding occurs in the initially still flat embryo. This two-part folding results in an enclosure of the endoderm by the ectoderm: In a first step, the laterally lying structures, due to the large and rapid growth of the internal embryonic anlage (especially due to the disintegration of the somites), are shoved in a ventral direction. Some of the structures lying in the middle are pressed against each other and fuse. The second step of the lateral folding has to do with the endoderm, from which the inner covering of the GI tract arises. The ectoderm of the caudal and cephalic ends of the embryo coalesce, due to the ventral folding along a medial line. As the amnion is pulled by the ectoderm, the small, dorsal amniotic cavity enlarges to surround the whole embryo. Amniotic cavity also surrounds the body stalk and the yolk sac— forming the umbilical cord. The endoderm, which becomes closed at both ends and along the embryo’s sides, forms a tube (future for-, mid-, hindgut). In the beginning the midgut stands in an open connection to the umbilical vesicle and the allantois—both of which are later taken up in the umbilical cord. The connection between the embryo and extraembryonic appending organs persists in order to permit the passage of the vital umbilical vessels which are located in the umbilical cord. The intraembryonic coelom, a cavity between the splanchnopleura mesoderm (outer covering of the intestines) and the somatopleura mesoderm (inner covering of the trunk wall)—which in the beginning is connected with the extraembryonic coelom (i.e., chorionic cavity)—becomes separated from it by the folding and fusion of the lateral sides of the embryo. Thereby, the intraembryonic coelom ring is formed.

The Cephalo-Caudal Folding (longitudinal direction)

In order to understand how this Folding of Cephalic End: Day 27 Folding of Cephalic End: Day 30 turning takes place, the structures must first be described that are found in the cephalic end before the folding: in the cephalic region, rostral to the prechordal plate and the pharyngeal membrane, the mesenchymal cells form the cardiac plate (pericardium) and the septum transversum (which later becomes a part of the diaphragm and separates the coelom into thoracic and abdominal cavities). With the 180° degree turn that 1 Future prosencephalon 6 Pharyngeal membrane results from the folding, the 2 Notochord 7 Extraembryonic mesoderm 3 Neural Tube 8 Throat following occurs: the pharyngeal 4 Pericardial cavity 9 Septum transversum membrane extends towards the lower 5 Cardiac tube front (mouth area) and the cardiogenic plate (which initially lay most cranially) into the thorax area. Between the cardiac anlage and the umbilical vesicle a mesenchymal bridge forms, the septum transversum [see pictures at upper right]. After this movement is completed, the brain (encephalon) lies the most cranially, followed by the mouth, heart, and diaphragm (septum transversum). During this folding the endoderm below the pharyngeal membrane becomes surrounded ventrally by the cardiac anlage. From this region, the throat (pharynx) arises and, subsequently, the thyroid gland, the lungs, and the esophagus. The pharyngeal membrane which, for now, separates the mouth (ectoderm) from the throat (endoderm) later atrophies. Folding of Caudal End: Day 27 Folding of Caudal End: Day 30 The folding of the caudal end occurs after the cephalic folding and has the result that the body stalk comes closer to the umbilical vesicle. Due to the large axial growth, the caudal end of the embryonic disk (with the cloacal membrane) comes to lie under the original embryonic disk and thus shoves the allantois and the body stalk in the ventral direction, up to the umbilical vesicle (yolk sac) and merges with its stalk 1 Notochord 1 Notochord 2 Neural fold 2 Neural Tube [see pictures to right]. 3 Amniotic cavity 3 Amniotic cavity The end of the primitive streak, 4 Primitive streak 4 Primitive streak which initially lies dorsally after the 5 Primary endoderm 5 Primary endoderm flexion of the embryo, now lies 6 Cloacal membrane 6 Cloacal membrane 7 Allantois 7 Allantois ventrally. 8 Body stalk 8 Body stalk 9 Hind gut

Development of the Placental Villi In order to understand the chronological development of the chorionic villi, it is important to have a comprehensive overview of placental anatomy. In this diagram, the placenta is roughly four months old and various fundamental structures can be recognized, namely the umbilical cord, the amnion, the chorionic plate, the already advanced branching of the villi, the basal plate and the cotyledon [see picture below].

Placenta at around four months

1 Umbilical cord 5 Basal plate 2 Amnion 6 Cotyledon 3 Chorionic plate 7 Villus 4 Intervillous space (maternal blood)

At birth, the placenta consists of two parts: maternal portion & fetal portion [see pictures below].

Maternal Portion / Side Fetal Portion / Side

1 Cotyledon 2 Cut edge of amnion 3 Umbilical cord 4 Decidua

http://embryology.ch/anglais/fplacenta/villosite03.html

Numerous "daughter" villi arise out of the tertiary villi. These remain either free and project into the intervillous space (free villi), or they anchor themselves to the basal plate (anchoring villi)

BEGIN AT MODULE 10, CHAPTER 2 (“THE CYTOTROPHOBLAST LATER”)

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