Medical Embryology - 2nd and 3rd Weeks

Germ discs and Gastrulation

Langman’s Medical Embryology, 13th Ed

Chapter concepts

1. Bilaminar and Trilaminar germ discs

2. Origin of the three embryonic “germ’ layers that make up the trilaminar disk

3.Describe the formation and derivatives of ectoderm, mesoderm and endoderm

Ⅰ. Gastrulation (Day 14 through Day 19)

- Formation of Mesoderm, Endoderm and Ectoderm

- At the caudal end, a midline indentation forms the primitive streak on the epiblast surface.

-  At the cranial end of the primitive streak is a slightly elevated region called the primitive node or knot which surrounds a small primitive pit.

- Cells of the epiblast proliferate and migrate toward and down through the primitive streak in a process called invagination.

- These invaginated cells subsequently detach and migrate underneath the epiblast.

- Some cells displace hypoblast cells to become the intra-embryonic endoderm.

-  Other cells take residence between the developing intra-embryonic endoderm and the epiblast to become the intra-embryonic mesoderm.

-  The epiblast layer is renamed the intra-embryonic ectoderm.

** NOTE The epiblast gastrulation gives rise to all three germ layers in the developing embryo

-Migration through the primitive streak continues until the end of the 4th week.

-The primitive streak then undergoes regressive changes and disappears.

-Distribution of intra-embryonic mesoderm

-invaginating cells which became intra-embryonic mesoderm spread both laterally and cranially

-  at oropharygeal membrane and cloacal membrane, two region of fused epiblast and underlying hypoblast (no mesoderm).

-Formation of the notochord

-  cells invaginating in through the primitive pit or knot form a solid rod of mesoderm, the notochord, that migrates cranically until it abuts the oropharygeal membrane.

-  The notochord serve as the basis of the axial skeleton in the midline and establishes right and left orientation.

-Changing shape of the germ disc

-  The embryonic disc is initially flat & round (Frisbee shaped)

-  It expands cranially and laterally to resemble a pear with subsequent elongation.

**NOTE: development and differentiation is usually more advanced at the cranial end of the embryo when compared to more caudal structures.

Ⅱ.Differentiation introduction

a.  Beginning of the third week--Gastrulation ensues transforming the bilaminar disc into a trilaminar disc composed of ectoderm, mesoderm and endoderm.

b.  Between the 3-8th weeks the growing gestation is called an embryo. During the “Embryonic period” the major body form and organ structure take shape. External and internal features become recognizable as human.

c.  The seven months following this period (the fetal period), the growing gestation is now called a “fetus” and development focuses on maturing the newly formed organs and tissues to a functional state.

Ectoderm Differentiation

a.  Neuralation

-  Ectoderm overlying the notochord, thickens to form the neural plate.

-  Lateral edges of the neural plate curve upward forming neural folds with a central neural groove.

-  Neural folds fuse at the future neck then progress cranially and caudally forming the neural tube, the future brain (cranial) and the spinal cord.

-  The anterior neuropore is the cranial opening of the neural tube, and the caudal opening- the posterior neuropore.

-  The anterior neuropore closes around day 25, the posterior neuropore around day 27.

-  Malformation can be associated with the closure of the anterior (anencephaly) or posterior (meningomyelocele) neuropores.

b.  Neural crest

-  Cells at the “crest” of the neural folds detach and migrates as the fold fuse.

-  These cells called neural crest cells migrate throughout the body to provide intermediate neural like cells to a variety of tissues, forming two lines of cell cords- ganglion.

c.  In summary, the ectoderm will give rise to

1)  The central nervous system (CNS): brain and spinal cord

2)  Neural crest cells will give rise to melanocytes, ganglion (PNS)

Note:

In general terms it may be stated that the ectodermal germ layer gives rise to those organs and structures that maintain contact with the outside world: (a) the central nervous system

(b) the peripheral nervous system

(c) the sensory epithelium of the ear, nose and eye

(d) the epidermis, including the hair and nails.

In addition it gives rise to: the subcutaneous glands, the mammary gland, the pituitary gland, and the enamel of the teeth.

Mesoderm Differentiation

-  initially loose

-  condensation day 17

Paraxial mesoderm, adjacent to the developing neural tube

a)  Cranial to caudal segmentation of the paraxial mesoderm => somites

20th days, 3 pairs /per day, 42-44 pairs by the end of 5th weeks

b)  Subsequent recognization and differentiation of somites into 3 region:

1.  Sclerotome—vertebra

2.  Myotome—will develop into the musculature of the region

3.  Dermatome—dermis of the overlying skin

Note of Figure:

Successive stages in the development of the somite.

(a)  The mesoderm cells are arranged around a small cavity.

(b) The cells of the ventral and medial walls of the somite lose their epithelial arrangement and migrate in the direction of the notochord. These cells are collectively referred to as the sclerotome.

(c) The dorsal somite will gives rise to a new cell layer, the myotome.

(d) After extension of the myotome in a ventral direction, the dermatome cells lose their epithelial configuration and spread out under the overlying ectoderm to form the dermis.

-  Intermediate mesoderm

-kidneys and genital system “Urogenital tissue”

-  Lateral plate mesoderm

- Separated by an intra-embryonic cavity=>the intra-embryonic coelom into

1.  Outer layer—Somite/parietal mesoderm, lines the parietal layer of the body wall (pleura, peritoneum, pericardium)

2.  intra-embryonic cavity—subdivided into peritoneal, pleural and pericardial cavities

3.  Inner layer—Splanchnic/visceral mesoderm, forming muscle, CT of gastrointestinal system, visceral layer of pleura, peritoneum and pericardium.

-  Mesenchyme: formation of blood and vessels

Ⅴ Derivatives of endoderm

-  The Gastrointestinal Tract

- During formation of the secondary yolk sac, proliferation and migration of the endodermal germ layer has provided an inner endodermal lining.

- Folding of the developing embryo incorporates a portion of the yolk sac into the embryo to form a endodermally lined tube

- The head and tail folds incorporate the foregut and hindgut, respectively

- The lateral folds produce the midgut which maintains contact with the yolk sac through the vitelline duct.

-Associated Organs

- Besides the gastrointestinal system, this endodermal tube will also contribute to the development of associated organs including

1) From the foregut: Thymus, Thyroid and parathyroid, Eustachian tubes and tympanic membrane, Lung, Liver & Pancreas

2) From the midgut: None

3) From the hindgut: Bladder and urethra

Ⅵ. Folding of the Trilaminar Embryonic Disc

a) During gastrulation cells are programed to become specific tissues. These

cells then migrate to specific locations within the embryonic disc.

b) Coordinated folding of the flattened disc is required to bring together these tissues to resemble the adult morphology. Some key landmarks

1. Oropharyngeal membrane - cranial fused 2 layered region (ectoderm and

endoderm) limiting the notochord => will become the future mouth

2. Cardiogenic region - cranial to the oropharyngeal membrane => will become the future heart and ventral chest

3. Cloacal membrane - caudal fused 2 layered region (ectoderm and endoderm) will become the future anus and genital openings

- Neuralation and cerebral development causes a uneven distortion of the developing neural tube along the cranial-caudal axis

a) Cerebral development causes the cardiogenic region and the oropharyngeal membrane, to fold ventrally

b) Similar caudal folding flips the cloaca and tissue to the cloaca ventrally inverting their orientation

- Somite and lateral plate mesoderm formation distorts the lateral aspects of the embryonic disc

1. This lateral folding pinches off a tube of the yolk sac to internalize the primitive gut

2. A transient connection with the yolk sac remains as the vitelline duct

- The complicated folding process puts the developing embryo in a vulnerable position making it susceptible to drugs that may change migration rates, cell proliferation or cell adhesion

- Clinical note of interest - by the end of the second month (8 wks) the form or

malformation of the embryo is established. Some young mothers may not even know they are pregnant yet.

Ⅶ Summary

-  During the embryonic period (3-8 weeks) the organs and the body shape are established

-  During this time the embryo is extremely sensitive to factors that can alter cell proliferation, cell adhesion and cell migration.

-  Chemicals that alter this balance and produce malformations are called teratogens.