Briefly describe Gastrulation
It begins with the formation of the primitive streak on the surface of the epiblast and is essentially the creation of three layers. Cells from the epiblast migrate towards the primitive streak and when they arrive, the break off, and dive under it, ending up between the epiblast and the hypoblast.
What controls the cells from the epiblast migrating towards the primitive streak?
FGF8 (fibroblast growth factor)—it downregulates E-cadherin
What are the specific names of the three layers formed?
The surface will be ectoderm, the middle layer will become mesoderm, and the hypoblast is replaced by the invaginating cells to become endoderm. The embryo then becomes a trilaminar disc
What is the source of all 3 layers?
What is the ectoderm and what does it differentiate into?
Connects to the “outside”. Produces the nervous system (peripheral and central), the epidermis (skin, nails, hair), sensory epithelium of the ear/nose/eye. Also produces subcutaneous glands, mammary glands, pituitary gland, and enamel of the teeth
What does the mesoderm differentiate into?
It’s the “middle”. Supporting tissue (cartilage, bone), muscle, blood and lymph cells, walls of the blood vessels and heart, genitourinary system, cortical portion of the adrenal, the spleen.
What will the connecting stalk eventually become?
the umbilical cord
What does the endoderm differentiate into?
It’s the “inside”. Epithelial lining of GI tract/respiratory tract/bladder/urethra, thyroid, parathyroid, liver, pancreas, lining of tympanic cavity and auditory tube
Gastrulation begins with the formation of the ___________.
True or false: once the primitive streak is formed on the surface of the epiblast there is now a head (cranial) and tail (caudal) end.
True; the cephalic end of the streak = primitive node
How are three layers created during gastrulation?
Cells from the epiblast migrate towards the primitive streak and when they arrive, they break off, and dive under it, ending up between the epiblast and the hypoblast. The invaginated cells become the endoderm and mesoderm while the cells remaining in the epiblast become the ectoderm.
What growth factor is key in gastrulation? What effect does it have on gene expression?
FGF8 is produced by streak cells and downregulates E-cadherin (binds epiblast cells together—thus the cells will become loose, break off and move) and it regulates Brachyury (T) which controls cell differentiation into mesoderm
Describe the migration of mesoderm.
Cells move into the primitive streak and then dive out to the edges in a predictable pattern depending on where they dove into the streak. For example, the cells that enter at the primitive node head straight up the middle (cranially).
Cells that migrate through the midline are also called what?
prenotochordal cells—they will form the prechordal plate and the notochordal process
Which of the three germ layers will form the spinal cord?
Discuss the formation of the definitive notochord
The prenotochordal cells initially become enmeshed in the hypoblast/endoderm forming the notochordal plate (like an “in between” stage). As the hypoblast is replaced by endodermal cells (moving in from the primitive streak), the notorchord plate gets pushed back up to form the definitive notochord
True or false: the notochord becomes the spinal cord
False; it more or less serves as a marker or “scaffolding” and then disappears; it’s been hypothesized that the nucleus pulposus is of notochordal origin
The notochord originates from which of the three germ layers?
Appearance of the notochord induces thickening of ectoderm leading to what structure?
Where is there a temporary connection between the ectoderm and endoderm? What happens if there’s a persistence of this connection?
the notochordal plate; if there’s a persistence of this connection (in other words, the notochordal process didn’t “bounch” back up) we get a neuroenteric canal
How does the neural plate form?
the appearance of the notochord induces thickening of the ectoderm which forms the neural plate. In other words, the notochord tells the overlying cells of the ectoderm to become the neural plate. The induction of the neuroetoderm is called neurulation
Describe the origin of the neural folds and their role in creation of the neural tube
The edges of the neural plate elevate and fold inward creating the depression known as the neural groove. The edges of the neural folds move towards the midline to fuse, creating the neural tube. NOTE: the cells at the crest of the neuroectoderm begin to dissociate from their neighbors and migrate throughout the body.
Where does the fusion of the neural folds first take place?
Folding starts at the 5th somite and then progresses both caudally and cranially
After the neural tube has formed, describe the spatial relationship of the ectoderm, neural crest, and neural tube
The ectoderm is on top of both the neural crest and neural tube (think of the skin over your spinal cord). The neural crest drapes over the neural tube.
Which neuropore will close first, the cranial or caudal?
the cranial neuropore will close first at day 25, while the caudal neuropore closes at day 27. Note: the closure of the neural tube is the final step in neurulation.
What pathology is associated with the failure to close the caudal neuropore
spina bifida and spina bifida occulta
What pathology is associated with the failure to close the cranial neuropore?
encephalocele and anencephaly
What is significant about the cells that sit at the crest of the neural fold?
They are designated neural crest cells and migrate away from the neuroectoderm to different parts of the body. For example, they can migrate to form melanocytes in the skin, sensory ganglion, or the cartilage/bone in the head.
What factor does the notochord secrete that is involved in inducing changes in the ectoderm.
Sonic hedge hog (Shh); as Shh is secreted from the notochord a gradient is formed
True or false: the notochord AND the neural tube are secreting Shh. If true, which specific part of the tube is secreting Shh?
True. The notochord and floor plate of the neural tube are secreting Shh.
What is the roof of the neural tube secreting?
Describe the gradient that the cells of the neural tube experience.
Cells experience different percentages of BMP and Shh depending on where they are in the neural tube. This gradient influences the cells’ differentiation
Explain why Shh is only expressed on the left side of the embryo
Shh is secreted throughout the primitive node initially. Subsequently, the Activin IIa
receptor is expressed on the right side of the node which blocks Shh expression. Shh is
thus expressed only on the left side of the node where it activates nodal and lefty
What is the sequence of maturation of the notochordal process?
Notochordal process → Notochordal plate → Notochord
What gene is expressed on the right side of the embryo?
What two genes are activated as a result of Shh on the left side?
Shh induces nodal, and then nodal induces lefty
What specifically does BMP4 do to the mesoderm?
it ventralizes the mesoderm (moves it toward the front of the embryo)
What 3 proteins are secreted to counteract BMP4? Where are they secreted from?
Chordin, noggin, and follistatin are secreted by the primitive node and block BMP4
which allows the notochord to stay dorsal.
What pathology is associated with mirror image of internal organs?
situs inversus; note: everything is still functional
What pathology is associated with a tumor that contains all three germ lines? What is
the most common location of this tumor?
Teratoma; most common location is saccrococcygeal. If it’s malignant it’s called a
yolk sac tumor.
What does the Brachyury (T) gene regulate in the embryo? What do deficiencies in
this gene cause?
It’s involved in the regulation of dorsal mesoderm formation in the mid and caudal
embryo. Deficiencies result in caudal regression.
What’s the most severe form of caudal regression syndrome?
Sirenomelia; note: has to do with regulation of dorsal mesoderm
What is a more common and less severe form of caudal regression
imperforate anus; note: has to do with regulation of dorsal mesoderm
The mesoderm that ingresses on the lateral edge of the primitive streak is called
What is the paraxial mesoderm responsible for forming? What are these structures?
Somitomeres; they are rounded structures that are paired and go on to form blocks of mesoderm called somites.
What day do somites start appearing on the embryo? Where do they start forming?
What is significant about their progressive formation?
Somites start around day 20 in the cervical region and 3 somite pairs are added per
day for the next 10 days. Because somites appear with specified periodicity, the age of
the embryo can be determined by counting the somites
Around the 4th week, ventral and medial walls of the somite loosen to become a ____.
What gene regulates somite differentiation into dermis?
What gene regulates somite differentiation into body wall and limb muscles
What gene regulates somite differentiation into back (epaxial) muscles
What does the sclerotome differentiate into?
Vertebrae and ribs
What does the dermomyotome differentiate into?
muscles/dermis under the epidermis
What layer does the dermis arise from?
Paraxial mesoderm (mid portion of dermatomyotome)
What portion of the dermomyotome becomes the expaxial (back) muscles
What’s unique about the origin of the bones of the face?
They are from the neural crest
What does the dorsolateral portion of the dermomytome become?
limb and body wall musculature
What week marks the end of the embryonic period and beginning of the fetal period?
What layer does the epidermis arise from?
The paraxial mesoderm gives rise to what paired structures?
Somites (which give rise to dermatomyotome and sclerotome)
What does lateral portion of dermatomyotome give rise to?
Body wall muscle
What does the sclerotome give rise to?
Bones and cartilage
The intermediate mesoderm is the origin of what structures?
What is the somatic/parietal mesoderm contiguous with?
Somatic extraembryonic mesoderm that covers the amnion
What is the splanchnic/visceral mesoderm contiguous with?
The splanchnic extraembryonic mesoderm covering the yolk sac
Which layer of the lateral plate mesoderm will cover the organs?
The splanchnic layer along w/ underlying endoderm will form wall of gut
Which layer of lateral plate mesoderm will form the lateral and ventral body wall?
What is the main organ derived from the endoderm?
What gets used up as fuel in formation of the gut?
What is the foregut composed of?
Anterior portion of endoderm (esophagus to ligament of Treitz)
What is the hindgut composed of?
Posterior portion of endoderm (mid transverse colon to anus)
What is midgut composed of?
In between anterior and posterior portion of endoderm (Ligament of treitz to mid transverse colon)