Riassunto esame Embryology (building bodies), Prof. Castagneti Lara, libro consigliato Carlson Embryology, Bruce M. Carlson

Formation of Amniotic Cavity and Yolk Sac

Formation of amniotic cavity:

It is one of the four extraembryonic membranes that form. The first cavity to be completely formed during the second week is the amniotic cavity, and it appears on the 8th day. A layer of epiblast cells expands toward the embryonic pole and differentiates into a thin membrane separating the new cavity from the cytotrophoblast. It expands steadily and by the 8th week, it encloses the entire embryo. It is dorsal in respect to the embryonic disc.

Formation of yolk sac:

A proliferation of hypoblast cells, followed by two successive waves of migration, forms the yolk sac membrane.

First wave of migration (8th day): forms the primary yolk sac (exocoelomic cavity) delimited by the Heuser's membrane and hypoblast cells.

Simultaneously, the extraembryonic mesoderm forms, filling the remainder of the blastocyst cavity with loosely arranged cells (believed to originate from the hypoblast/primary yolk sac, but...)

The trophoblast may contribute cells as well.

SECOND WAVE OF MIGRATION (12 DAY)

Second wave of migrating hypoblast cells, which form the secondary yolk sac.

From the splitting of the extraembryonic mesoderm in two layers, the extraembryonic coelom or chorionic cavity forms. The chorionic cavity helps separating the embryo – with its amnion and yolk sac – from the outer wall, the chorion.

Formation of connecting stalk

On days 12-13, the extraembryonic mesoderm divides into two layers, effectively changing also the yolk sac and amnion (they also become two-layers structures).

Made of extraembryonic mesoderm and endoderm

Made of extraembryonic mesoderm and ectoderm

By day 13, the embryonic disc with its dorsal amnion and ventral yolk sac is suspended in the chorionic cavity solely by a thick stalk of extraembryonic mesoderm (= connecting stalk).

Traditionally the cavity of the yolk sac has been defined as the yolk sac (or exocoelomic cavity) and its membrane exocoelomic membrane/Heuser’s membrane.

Letizia Hassan

Definitive yolk sac forms after formation and splitting of the extraembryonic mesoderm. It is a two-layered structure consisting of hypoblast-derived endoderm on the inside and mesoderm on the outside. It remains a major structure associated with the developing embryo through the 4th week and performs important early functions. The outer layer (extraembryonic mesoderm) is an important site of hematopoiesis - the wall of the yolk sac is an important site for proliferation of PGCs. After the 4th week, the yolk sac is overgrown by the developing embryonic disc. If the yolk sac doesn't disappear, it could remain after birth in the form of a digestive tract anomaly (Meckel's diverticulum).

Uteroplacental circulatory system begins to develop during the second week. During the first week of development, the embryo obtains nutrients and eliminates waste by simple diffusion. Rapid growth makes a more efficient method of exchange imperative - uteroplacental circulation.

(its formation starts on day 9)HOW: system by which maternal and fetal blood flowing through the placenta come into proximity and exchange gases and metabolites by diffusion.

Formation: In the area of trophoblastic lacunae (inside the syncytiotrophoblast), maternal capillaries near the syncytiotrophoblast then expand to form maternal sinusoids, that rapidly anastomose with the trophoblastic lacunae. Between days 11-13, as these anastomoses continue to develop, the cytotrophoblast proliferates locally to form extensions (they grow into the overlying syncytiotrophoblast). These grow out into the blood-filled lacunae, carrying with them a covering of syncytiotrophoblast.

RESULT: primary chorionic stem villi. It is not until day 16 that the extraembryonic mesoderm associated with the cytotrophoblast penetrates à the core of the primary stem villi result: secondary chorionic stem villi.

By the end of the 3rd week, this villous mesoderm has given rise to blood vessels that connect with

The vessels forming in the embryo proper. Villi containing differentiated blood vessels are called tertiary chorionic stem villi. Gases, nutrients and wastes that diffuse between the maternal and fetal blood must cross four tissue layers:

1. A layer of syncytiotrophoblast
2. A layer of cytotrophoblast
3. The loose C.T. in the core of the villus (extraembryonic mesoderm)
4. The endothelium of villus capillaries.

Miscarriage is pregnancy loss that occurs naturally before the 20th week of gestation:

• Most common during the third week after fertilization (25-30% of recognized pregnancies end in miscarriage)
• Frequency of early spontaneous abortion is difficult to assess because it is often mistaken for a delay in menstruation
• More than 50% of known spontaneous abortions result from chromosomal abnormalities

Also, failure of the blastocyst to implant (ex. the endometrium is inflamed). When the embryo has developed more, abortion incidence is due to neural tube defects, cleft lip, or cleft.

After the 10 gestational week, 25-40% of spontaneous abortions are related to fetal causes, 25-35% to placental causes, 5-10% to maternal causes.

THIRD WEEK, BECOMING TRILAMINAR (GASTRULATION) AND ESTABLISHING BODY AXES

GASTRULATION

It is the process that transforms the bilaminar embryo made by epiblast and hypoblast into a trilaminar embryo.

Formation of primitive streak

On about day 15 of development, a thickening containing a midline groove forms along the midsagittal plane of the embryonic disc (now has an oval shape). This thickening (= primitive streak), elongates to occupy about half the length of the embryonic disc, while the primitive groove becomes deeper.

The cranial end of the primitive streak is expanded in a structure called the primitive node. The node contains a depression (primitive pit), which continues caudally with the primitive groove.

Formation of the primitive streak defines all body axes it forms at the caudal midline of the embryonic disc.

thus defining the CRANIAL-CAUDAL AXIS, and MEDIAN-LATERAL AXIS. Because the formation of the primitive streak occurs at the midline, when the epiblast is viewed looking down at it from inside the amniotic cavity and facing its cranial end, what lies to the right will be the right side of the embryo and vice versa (thus defining the left-right axis). During gastrulation epiblast cells move toward the primitive streak, enter the primitive streak, and àthen migrate away from it as individual cells (= ingression). During the epithelial – mesenchymal transition (EMT), the primary mesenchyme cells (PMCs) detach from the epithelium and become internalized mesenchyme cells that can migrate freely. This transition is guided by a lot of molecular factors (ex. fibroblast growth factor). EMT CHANGES: The changes that take place in the cells concern the communication between cells (from cell-to-cell to cell-to-substrate adhesion) and the shape and cytoskeletal organization of the cell (they form

cytoplasmic projections).1 It may also happen in cells of adult tissues, this may cause erosion of basal membrane and even carcinogenesis. 25Letizia HassanRepression of epithelial featuresSome genes for epithelial features(such as the ones for junctions orcell polarization) can be repressed.Ex. as we want to repress the pieceof gene that codes for e-cadherin(important molecule in celljunctions), we will use thetranscription factor Snail (binds to the DNA portion that expresses e-cadherin and represses itsproduction).à Snail is under the control of other factors, such as the fibroblast growth factor (FGF), the signalingfactor (WNT), the morphogenetic protein (BMP), the tumor growth factor beta (TGF-beta) andothers. It also induces the production of vimentin inside the cytoskeleton.Problems during gastrulation may lead to severe conditions and physical defects.àSirenomelia rare condition occurring in 1 in 70,000 births. The most obvious defect is a fusion ofthe two lower

limbs at the midline; most babies die within a few days of birth. This condition also brings anomalies in digestive, urinary and genital tracts

Conjoined twins

Situs inversus The body is completely mirrored symmetrically due to problems during the formation of left-right asymmetry; usually, it is clinically irrelevant, but it may also lead to Kartagener syndrome (infertility, problems at respiratory system…).

Formation of definitive endoderm takes place on day 16.

The epiblast cells start undergoing EMT in the primitive streak.

EMT: Sheet of regularly shaped cells MESENCHYME(often cuboidal) interconnected to Irregularly shaped and loosely one another at their cell surfaces connected cells

EMT takes place thanks to the formation of thinner processes called filopodia and flattened processes called lamellipodia, which allow cells to migrate through the primitive streak into the space between epiblast and hypoblast.

the first ingressing epiblast cells invade the hypoblast and

displace its cells, the new hypoblast is completely replaced by a new layer of cells, the definitive endoderm. Mesodermal migration thOn the 16 day the second wave of migration of the epiblast cells migrates through the primitive streak and starts to spread in between the endoderm and epiblast, forming the intraembryonic mesoderm (or mesoderm mesenchyme). 26 Letizia HassanThey all take different pathways of migration: some remain close to the midline, some migrate rostrally… à 2 FAINT DEPRESSIONS ARE EXCEPTIONS: where the endoderm and the future ectoderm are really attached with no mesoderm in between (thin areas) à1. Oropharyngeal membrane, cranial it will break down to form the opening to the oral cavity à2. Cloacal membrane, caudal it will degenerate to form the openings of the anus and urinary and genital tracts. The notochord thIts formation begins on the 17 day with cranial midline extensions from the primitive node of a hollow tube, the notochordal process. This tubeown to form the notochordal canal. This canal serves as a temporary support structure for the developing embryo. 2. The notochordal cells undergo a process called vacuolation, where fluid-filled spaces form within the cells. This allows for flexibility and movement of the notochord. 3. The notochordal process elongates and extends from the primitive node towards the future head region of the embryo. This process helps to establish the body axis and provides a signaling center for the development of surrounding tissues. 4. The notochordal process eventually becomes the notochord, a rod-like structure that runs along the midline of the embryo. The notochord plays a crucial role in patterning the embryo and influencing the development of various organ systems. Overall, the formation and elongation of the notochord is a critical step in early embryonic development. It helps to establish the body axis and provides important signals for the development of surrounding tissues.