Creating Bodies
Implantation, Invagination, Gastrulation, Organ Formation, Neurulation, Cephalization
By: Aditi Mankodi, Maria Saraf, Anupama Singh

A week after fertilization, the dividing zygote reaches an embryonic stage called the blastocyst. The blastocyst, a sphere of ball with cells and a cavity, implants in the endometrium, the inner membrane of the uterus. During implantation, the blastocyst not only becomes embedded in the endometrium, but the endometrium also then grows over the blastocyst. After implantation the differentiation of the cell mass begins (5)

Journey of the fertilized egg
Journey of the fertilized egg

Implantation Stages
There are three stages of implantation: apposition, adhesion and invasion. In the first stage, apposition of the blastocyst and the uterine mucosa, a region of the uterine wall where normal implantation occurs, takes place. This can only occur in the period of time known as the “implantation window”. (3) This reception-ready phase of the endometrium lasts 4 days, and comes 6 days after the LH peak. In this stage the blastocyst can still be eliminated by being flushed out. (1)

A. Menstruation B. Proliferation C. Secretion D. Implantation window
A. Menstruation B. Proliferation C. Secretion D. Implantation window

After the blastocyst and the endometrium are in close proximity, microvilli on the surface of the outermost trophoblast cells interact with the epithelial cells of the uterus. The adhesion of the blastocyst on the endometrium arises through cell surface glycoproteins, a process still not well understood. At this stage, the blastocyst cannot be flushed out. (1)

As soon as the adhesion on the endometrium is complete, the trophoblast (the cells on the outside of the blastocyst) gets to work and differentiates into two types of cells, ST (syncytiotrophoblast) cells on the outside and CT (cytotrophoblast) cells on the inside. The lytic activity of the ST cells causes the endometrium to erode to provide a place for the embedding of the blastocyst. (3) As implantation progresses, the ST cells quickly surround the embedded embryo. Maternal vessels eroded from ST cells’ lytic activity helps provide the growing embryo with maternal blood and a “primitive utero-placental circulatory system is thereby engendered” (“6.7 Brief Summary”) at around the 13th day. (1)

(1) Gradual apposition of blastocyst to endometrium. (2) Interactions between the blastocyst and endometrium lead to adhesion. (3) Adhesion induces reaction in trophoblast cells to differentiate into St and CT cells. (4) Trophoblasts produce HCG which stimulates corpus luteum to produce progesterone. This conserves the pregnancy. Implantation is complete.
(1) Gradual apposition of blastocyst to endometrium. (2) Interactions between the blastocyst and endometrium lead to adhesion. (3) Adhesion induces reaction in trophoblast cells to differentiate into St and CT cells. (4) Trophoblasts produce HCG which stimulates corpus luteum to produce progesterone. This conserves the pregnancy. Implantation is complete.

Control of the Blastocyst Implantation

For blastocyst implantation, interaction between the embryo and uterus is needed. This process involves the trophoblast cells interacting with the endometrium, and can only take place during the “implantation window” which spans from 20-24 days of the menstrual cycle. (4) Initially it is dependent on the levels of progesterone and estrogen, but later chemical signals from the embryo and the trophoblast lead to further morphological and biochemical changes. (4) At any other time, the epithelium of the uterus is covered by thick glycocalyx, a transmembrane glycoprotein that has an extended extracellular matrix which prevents blastocyst attachment. Blastocyst attachment to the uterine wall also depends upon the interaction between adhesion molecules expressed on both trophoblast cells and uterine epithelium. This interaction is mediated, in most cases, by bridging ligands which are released in the uterine cavity. (4)
Control of Blastocyst Implantation
Control of Blastocyst Implantation

Cytokines, small cell-signaling protein molecules used in intercellular communication, and chemokines, cytokines that act as a chemo-attractant to guide the migration of cells, both play a role in the control of the human blastocyst implantation. The molecular mechanisms of implantation involve “complex cascade-like interactions between the embryonic trophoblast cells, epithelial cell, decidual cell, cells responsible for immune reactions and the extra-cellular matrix (ECM) of the maternal endometrium.”(2)
Decidual cells are enlarged cells found in the uterine mucous membrane and they specialize to provide the embryo with nutrients. The decidual cells and the endometrial glands, along with the embryo, secrete growth and other factors that facilitate the implantation of the embryo.(2) "Moreover chemokines, interacting with G protein-coupled receptors, induce a structural change in integrins which favors adhesion of the blastocyst to the decidualized endometrium." (4)

The molecular interactions between the blastocyst and the uterus happen in three stages:

1) Signal exchange during the preimplantation
2) Adplantation: Interactions between the blastocyst and the uterine epithelium
3) Invasion of the trophoblast: Interactions between the blastocyst and the endometrium (2)

1. Signal Exchange during preimplantation

Even before apposition, the embryo and the endometrium communicate. When the blastocyst emerges, it secretes molecules that affect the ovary, the fallopian tubes and the endometrium. Receptors appear on the blastocyst for factors such as the leukocyte inhibitory factor (LIF). The embryo also produces interleukin 1, a type of cytokine, which helps orient it toward the endometrium. During preimplantation, the density of glycocalyx (thick surface proteins), along with the electrostatic repulsion between the blastocyst and the endometrium, decreases and helps implantation. (2)

2. Adplantation: The Blastocyst and the Uterine Epithelium

The apposition and the adhesion of the blastocyst require secretions of numerous factors such as interleukin 1 (IL-1), the inhibition factor for leukocytes (LIF) and the epithelial growth factor (EGF). These factors, secreted by either the blastocyst or the uterine epithelium, bind to receptors of the other tissue. (2)During implantation, LIF is made by the uterine epithelial cells and its receptors are on the blastocyst. “It appears to play a role in the differentiation of the CT to ST and assists HCG (human chorionic gonadotropin) secretion.” (2) The receptors for EGF are expressed by the blastocyst. However, these receptors appear in the inner cell mass and the trophoblast at different times, which explains the orientation of the blastocyst that causes it to embed in the endometrium with the appropriate side. (2)

Cell Signaling in Adplantation
Cell Signaling in Adplantation

3. Invasion of the Trophoblast: The Blastocyst and the Endometrium
The trophoblast infiltrates the endometrium by secreting enzymes that makes the extra cellular matrix (ECM) more porous, and by growing into the decidua of the uterine tissue, which is the uterine lining. (2)Trophoblast cells express certain cell adhesion molecules (integrins) on their membranes that interact with the uterine membrane. Endometrial factors greatly facilitate the growth of the trophoblast into the endometrium by using autocrine (self-signaling) and paracrine (chemical signaling) cells. These ease the invasion of the trophoblast.(2)

Invasion of the Trophoblast
Invasion of the Trophoblast

Abnormal Implantation

There can be many different causes for abnormal implantation. Besides the normal implantation zone, there are other locations, both within and outside the uterus, where the blastocyst can embed itself. This is called extra-uterine gravidity (EUG), where the fertilized egg settles outside the inner lining of the uterus. (3) “When the implantation takes place in the lower part of the uterus, the placenta will later develop in the cervix uteri” (“6.7 Brief Summary”). This type of implantation is called placenta previa, and it can lead to serious complications (hemorrhages). (3)

Abnormal Pregnancy (Ectopic Pregnancy)
Abnormal Pregnancy (Ectopic Pregnancy)

Invagination is when the cells in the blastocoel cells flatten slightly to form a vegetal plate that buckles inwards. The vegetal plate then undergoes extensive rearrangement of its cells, a process that transforms the shallow invagination into a deeper pouch called the archenteron, which is a primitive gut. The open end of the archenteron, which will become the anus, is called the blastopore. Outside of embryonic development, invagination happens to the outer layer of cells in an organism so they form a pocket in the surface, which makes room for more cells to reproduce. Basically, invagination is the infolding of cells to form new cells. (13) It is like the formation of the cleavage furrow during cytokinesis in animal cells. For example, the inner membrane of a mitochondria invaginates to form cristae, making a greater surface area to accommodate the protein complexes and other objects that help produce ATP. Another example is when invagination happens in part of the intestine, which is called intussusception. Invagination is the morphogenetic process by which an embryo takes form and is the initial step in gastrulation. Gastrulation turns the blastula into a multi-layered organism with the three different germ layers. Localized invaginations also occur later into embryonic development to form the coelom. Invagination also occurs during endocytosis and exocytosis when a vesicle form within the cell and the membrane closes around it. (12)

An example of how invagination works
An example of how invagination works

McGraw Hill animation
This animation explains the process of endocytosis and exocytosis. The infolding of the cell in this process happens because of invagination.

Gastrulation is a development in multicellular animals where there is a dramatic rearrangement of the cells of the blastula (aka blastocyst) to form the gastrula (a hollow, two-layered sac that consists of the ectoderm and the endoderm). It takes place after cleavage and is followed by organogenesis (17). At the end of the second week of development, the cells of the blastocyst, a ball of cells that contains a fluid filled cavity, begin to differentiate into the three main germ layers: endoderm, mesoderm, and ectoderm (15). The cells of these three layers eventually differentiate into specialized tissues and give rise to various organs. The three main developments that occur during gastrulation are: 1) The establishment of the three primary germ layers 2) The establishment of the basic body plan 3) The movement of cells to different locations - this allows for new cell interactions such as inductive interactions (when a signal passed from one cell(s) causes the other cell(s) to change their fate). The inductive interactions are important for other developments such as organogenesis and neurulation (14).

Gastrulation varies depending on the organism; however there are common set of cellular mechanisms: changes in cell motility, changes in cell shape, and changes in cell adhesion to other cells and to molecules of the extracellular matrix.

Gastrulation in Mammals
Gastrulation in Mammals

The Three Germ Layers
1. Ectoderm - this is the outermost layer that forms first. The cells of the ectoderm differentiate (become more specialized) into the integumentary system (skin and all its derivatives) and all the neural tissue. The three parts of the ectoderm are: external ectoderm (skin, etc.), neural crest, neural tube (both of which are formed during neurulation).
2. Endoderm - this is innermost layer and is the second to form. The cells differentiate into the majority of the endocrine system, epithelia (tissue that lines the cavities and other various structures throughout the body) of the lungs and of the gastrointestinal (digestive) tract.
3. Mesoderm - this middle layer that fills the space between the other two layers is the last to form and its cells specialize into almost all of the components of the skeletal system, all muscle tissue, and all components of the cardiovascular system (including bone marrow).

external image 1-s2.0-S009286740800216X-gr1.jpg

An Example of Gastrulation in Frog Embryo
1. Gastrulation in the frog blastula begins when a dorsal lip (a fold of the blastula) appears -- this small change in shape occurs as a result of the cells changing shape and pushing inward. The future endoderm and mesoderm cells roll inward over the dorsal lip (involution) and move into the interior of the gastrula. The future ectoderm cells spread over the outer surface.

2. The lip of the blastopore starts to become circular. The three germ layers start to form as cells migrate inwards and start to fill the space of the blastopore that was originally occupied by the blastocoel.

3. The circular blastopore surrounds the yolk plug (yolk cells). The yolk cells move inward as the ectoderm expands and the blastopore shrinks. The germ layers are now ready, and organogenesis happens.

Diagram displaying the process of gastrulation in frog embryos.

An organ is a specialized section of the body composed of several different types of tissues. Organogenesis is the formation of the different organs from the three germ layers: ectoderm, endoderm, and the mesoderm. The three kinds of morphogenetic changes (folds, splits, and dense clustering of cells) are usually the first evidence of organ formation. Early organ formation in vertebrates includes the formation of the notochord by condensation of dorsal mesoderm, development of the neural tube from folding of the ectodermal neural plate, and formation of the coelom from splitting of the lateral mesoderm. The three germ layers will eventually differentiate into various organs. The endoderm cells specialize into the lining of the digestive system, the lining of the respiratory system, the liver, the pancreas, thyroid, parathyroids, thymus, lining of the urethra, urinary bladder, and reproductive system. The ectoderm cells makes the skin and its derivatives, the lining of the mouth and the rectum, the sensory receptors in the epidermis, cornea and the lens (parts of the eye), the nervous system, adrenal medulla, tooth enamel, the pineal and pituitary glands. The mesoderm cells make the notochord, skeletal system, muscular system, circulatory and lymphatic systems, the excretory systems, parts of the reproductive system (except the actual germ layers), dermis of the skin, the lining of the body cavity, and the adrenal cortex. Vertebrate ectoderms have three parts: the external ectoderm, the neural crest, and the neural tube (the second and third is eventually known as neuroectoderm). The external ectoderm makes most of the stuff that originates from the ectoderm (ex: skin, mouth, nasal cavity, tooth enamel, pituitary glands, parts of the eyes, and other stuff). The neuroectoderm makes the lining of the nervous system and the brain. The endoderm and the meosderm do not split into various parts until they begin to form the individual organs. (10, 13)

Some Highlights of Organ Formation During Embryonic Development (9)
  • At six weeks the embryo begins to form the pulmonary primordium which is the first trait of a lung. The hepatic plate is also formed which is the beginning of the liver
  • At week eight the actual lungs begin to develop and the lymphatic system also begins to develop
  • By week nine most of the vital organs have begun to form and will continue to develop
  • Between thirteen and sixteen weeks the fetus' pancreas and liver produce fluid secretions
  • By week twenty the fetal heartbeat can be heard by a stethoscope
  • By week 23 the alveoli have formed and the by week 27 gas exchange is possible even if the respiratory system is still developing

Close up: Heart Formation
The rudimentary heart in vertebrates develops from the vental edges of the mesodermal mantle in the anterior part of the body. Some mesodermal cells break away from the ventral edge of the lateral plate. They position themselves under the endoderm and then arrange in the form of a thin walled tube, which will become the endocardium, the lining of the heart. The mesoderm actually breaks into two parts called the myocardium and the endocardium. These cells make a heart tube that is formed along the anterior/posterior axis for the chambers of the heart. The heart tube folds to make five dilations of the primitive heart which will eventually develop into the adult heart. To make these five folds, the heart goes through looping, the folding of the tube from left to right. Until the heart is done looping, the different parts of the heart cannot be differentiated. Then a primitive atrium and bentricle form along with the pulmonary and systemic veins and arteries. The heart continues to form as the fetus develops more. (11)

Representation of Organogenesis
Representation of Organogenesis

A table representation of what the different germ layers make during organ formation
A table representation of what the different germ layers make during organ formation

Neurulation is a main part of organogenesis that occurs in vertebrate embryos. The process begins after the neural plate has been formed, and its key products are the neural tube and neural crest cells. The neural tube forms the brain and the spinal cord, and the neural crest cells migrate to other parts of the body and form various aspects of the peripheral nervous system such as the skull and jaw. These cells also give rise to a variety of other cells types including pigment cells and neurons.

HOW THE NEURAL PLATE IS FORMED: The notochord, a flexible rod shaped body that is found in the embryos of all chordates, helps ensure proper neural plate formation. It signals the ectoderm germ layer to form a thick, flat neural plate (the thickening of the ectoderm occurs, which is caused by the thickening of the epithelial cells). The 3 inhibitory signals - chordin, noggin, and follistatin - are needed to form this neural plate (16).

A Simplified Version of Neurulation
A Simplified Version of Neurulation

Neurulation consists of two main parts: primary and secondary neurulation.

Primary Neurulation
Primary neurulation divides the ectoderm into three main parts: (1) neural tube - internally located (2) epidermis - externally located (3) neural crest cells - develop between the neural tube and epidermis and then migrate to different places (16).

During primary neurulation, the neural plate folds into the neural tube. The process begins after the neural plate has been formed, and it is initiated when the notochord secretes various growth factors that cause the cells to undergo shape changes which in turn result in the folding of the plate. The edges of the plate lift up to form the neural folds, which then pinch together to form the epidermis located above the neural tube. The neural plate fuses together to create the actual tube. In addition to the neural folds, the neural plate also creates the neural groove - a shallow groove between the neural folds of the embryo (15). As the neural folds/plate continue rising and becoming circulated to eventually form the epidermis/tube, the groove deepens, and when the folds meet and fuse together, the groove is converted into the closed tube. The cells surrounding the neural plate direct the neural plate cells to proliferate, invaginate, and pinch off from the surface to form a hollow tube. The bona fide epidermis is created by the folds (16).

After the neural tube has been formed, the cells of the notochord are then fated to die (apoptosis).

Neural Crest Cells: As mentioned previously, these important cells are migratory and specialize into various "things." They are created at the border of the neural plate (near the neural folds) after gastrulation. After the neural tube has finished closing, the cells undergo a transition that allows them to migrate and differentiate into varied cell types. (Numerous transcription factors and interacting signals play a role during the formation, migration, and differentiation of the neural crest cells).

Note: the neural crest itself is just a mass of tissue (16).

An example of the numerous "things" the crest cells differentiate into
An example of the numerous "things" the crest cells differentiate into

Secondary Neurulation
During this stage of the process, the neural ectoderm and some cells from the endoderm form the medullary cord, a part of the medulla of the lymph node that contains lymphatic tissue - B cells and plasma cells are the main types of cells found here. This cord then condenses and forms cavities which then merge together to form another tube. The tubes from both stages of neurulation connect to form one big neural tube which then specializes into the brain and the spinal cord as the embryo grows.

In other words, the cells of the neural plate itself form another cord-like structure which then migrates inside the embryo and hollows to form a tube. This process occurs in the posterior section of most animals (15).

Problems with Neurulation
During this complicated process, various problems can occur. The neural tube defects, as opposed to the neural crest cell defects, are the most common (occurring in about 1 out of 500 births).

1. The neural tube first closes in the middle and then moves anteriorly and posteriorly - if the tube doesn't start closing anteriorly, it causes anencephaly. The anterior part of the tube grows to become the cerebrum. If this part fails to fuse, it results in parts of the brain remaining unfused as the embryo matures, and therefore causes the degeneration of the skull and forebrain. Babies with this condition are either stillborn or die shortly after birth.

A front view of an anencephalic fetus
A front view of an anencephalic fetus
external image anencephaly1.gif

2. If the tube doesn't close posteriorly, it results in a spina bifida - a part of the spinal cord sticks out through the opening in the bones. In its most severe form, this condition is characterized by the failure to form the neural plate. Spina bifida can also result in paralysis beneath the affected region of the spinal cord, forcing the afflicted to use crutches or wheelchairs. Some paralysis of the legs is common.

external image Spina_Bifida-1.jpg external image 19087.jpg

Cephalization, associated with bilateral symmetry, is when sensory organs and systems move to the anterior end of an animal. It also includes the development of the central nervous system, which includes the brain and the spinal cord. (5) Cephalization evolved many times within the animal kingdom, suggesting its importance. The emergence of Cephalization let to the ‘head’ of the animal becoming the first to encounter food, water, predators and other important external stimuli of its environment. (8)Scientists have found that cephalization might have evolved in a very ancient time. Genes that determine that the head becomes a separate region from the body are present in many different animal phyla, even in the cnidarians. This indicates that these genes relating to cephalization were present in the ancestor of most of the animals and must have evolved long ago.(8)

Organisms with and without cephalization
Organisms with and without cephalization

Cephalization in the Animal KingdomSome of the most primitive creatures, such as the cnidarians, have some form of cephalization. At their ‘heads’, they have photoreceptive cells and a collection of neural cells that help the animal detect its surroundings. Another phylum demonstrating cephalization is platyhelminthes, which includes organisms such as flatworms and tapeworms. Flatworms have sense organs, such as photosensory and chemosensory cells, at their anterior ends, which shows how cephalization plays a role in this organism. However, flatworms differ from other “advanced animals in that their mouths are in the center of their bodies, not at the anterior end.” (8) Since such ancient organisms show evidence of cephalization, scientists believe that it evolved early in the divergence between bilaterally symmetrical organisms and radially symmetrical organisms. In other more advanced animals, such as the arthropods, cephalization evolved more segments of the head and the formation of the mouth. (8) Since cephalization combined activities of the nervous system, it would have been beneficial that the head became separate from the body and had a feeding mechanism as well as receptors for other environmental stimuli.

Cephalization in a flat worm (Phylum Platyhelminthes)
Cephalization in a flat worm (Phylum Platyhelminthes)

Starting from the platyhelminthes, cephalization followed an evolutionary trend and culminated in the advanced, complex nervous system of vertebrates. Vertebrates have many distinct features at the anterior end, and all the features work together to help the organism understand its environment through the various structures, such as the sense organs (eyes, ears etc), that respond to different stimuli.
The vertebrate head resulted from the evolution of previously existing models; however, the cells that give rise to the important features of the vertebrate head, neural crest cells (embryonic cells), are found only in vertebrates. This suggests that the vertebrate head has evolved much from its ancestral form and now has diverged to a point where the cells that lead to it are no longer the same as those before it. The neural crest cells arise from the ectodermal layer, one of the three layers of cells emerging from the changing blastocyst that leads to all the organs of a vertebrate.(8)

The neural crest cells lead to a diversity of features on the vertebrate head through their flexibility, and give rise to the facial bones, jaws, the tongue and the teeth.
Scientists think that the increased sophistication of cephalization in vertebrates, such as the formation of a jaw and a large brain, correlates with better adaptation for predation. These sensory organs help vertebrates find and successfully hunt prey. (8)

Losses of CephalizationSome groups have lost cephalization, while others have gained it. An example of losing cephalization can be seen with the phylum echinodermata, which includes creatures such as starfishes and sea urchins. These species “have lost bilateral symmetry and returned to a radially symmetrical body plan.” (8) However, the larval stages of these organisms have bilateral symmetry. In the adult form echinoderms have radial nerves that run the course of their bodies, and a rind of nerves that surround the gut. They also don’t have any specialized sense organs, but instead have just sensory neurons located on the ectoderm. (6)

Some echinoderms
Some echinoderms

Mollusca is an interesting phylum, in that this group demonstrates the loss and regain of cephalization. Mollusca includes a wide variety of organisms, ranging from squids and octopuses to snails and slugs. In the Class Bivalvia, organisms have lost cephalization and their nervous systems are much reduced and limited to unrefined chemosensory organs, locomotion mechanisms and feeding mechanisms. (7) However other Mollusks, in particular the octopuses and squids, have a high degree of cephalization and nervous system development. They have well developed brains and eyes, and along with their other sense organs, these are concentrated in a distinct head region. These characteristics, similar to the vertebrates’, evolved as a predatory adaptation. (7)

The Classes in Mollusca
The Classes in Mollusca
An Octopus (Class Cephalopods)
An Octopus (Class Cephalopods)

A Scallop (Class Bivalves)
A Scallop (Class Bivalves)

1. __ Implantation Stages
2. Aspects of Implantation
3. __ of Implantation
4. __ of the Trophoblast in Blastocyst Implantation
5. Campbell, Neil A., and Jane B. Reece. Biology. Sixth ed. Boston, MA: Pearson Custom/Benjamin Cummings, 2002. 637, 990. Print.Definition of Implantation and Cephalization
6. __ in Echinoderms
7. __ in Mollusca
8. __ in the Animal Kingdom
9. __
A brief overview of how organ formation happens

10. __
Talks about the germ layers and what they form (specifically the endoderm)
Talks about how organ formation happens during embryonic development
12. __
Brief overview of what invagination is
13. Campbell, Neil A., and Jane B. Reece. Biology. Sixth ed. Boston, MA: Pearson Custon/Benjamin Cummings, 2002. 637, 1005. Print.
Definition of the three germ layers and invagination
14. __
The main developments of gastrulation
15. __
Important information on both gastrulation and neurulation
16. __
Step by step process of neurulation
17. __
Detailed process of the development of the embryo
1. During this four day period where the blastocyst implantation can occur,
a) The surface proteins (glycocalyx) decrease in density
b) The electrostatic force between the blastocyst and the epithelial cells increase
c) Only the blastocyst secretes chemicals that are detected by the receptors in the uterus
d) The ST cells erode the maternal blood vessels for the growing embryo
e) Both A and B

2. In an ectopic pregnancy
a) Tubal or cervical pregnancies can occur
b) The blastocyst settles in the uterine lining
c) The fertilized egg does not mature into a blastocyst, yet it still implants
d) The blastocyst splits in half and results in two implantations
e) The cause is the failure to divide properly

3. The development of the nervous system is important in cephalization because
a) The sense organs migrate towards the anterior region in cephalization
b) The nervous system controls many aspects of cephalization
c) Cephalization combines the activities of the nervous system in radially symmetrical organisms
d) All organisms with a nervous system go through cephalization
e) Both A and D

4. Which of the following options are correctly paired together?
a) Ectoderm – last germ layer to form
b) Mesoderm – the chemical that stimulates the growth of neural plate
c) Ectoderm – the outer germ layer that is the first to develop
d) Endoderm – forms the neural tissue
e) Both A, B, and D

5. When neurulation fails to occur correctly, the organism
a) Can be paralyzed
b) Can die
c) Is fine because the defects can be corrected later
d) Has a functioning brain with minor issues
e) Both A and B

6. Gastrulation and neurulation are related because
a) Gastrulation provides the germ layers whose cells will later form the products of neurulation
b) Gastrulation is the beginning of the neurulation process
c) During gastrulation, cells are rearranged and new interactions occur, which is important for processes like neurulation
d) Neurulation is the step that immediately precedes gastrulation and it lines the tissues up properly in order for gastrulation to occur e) Both A and C

7) Put the following stages in order to correctly show the formation of the heart in the embryo:
1. the heart goes through looping
2. the ventricles and atria develop
3. the mesoderm breaks into two parts (endocardium and myocardium)
4. the pulmonary and systemic systems form
5. the heart tube forms
a) 1, 2, 3, 4, 5
b) 3, 5, 1, 2, 4
c) 3, 5, 2, 1, 4
d) 2, 3, 1, 4, 5
e) 1, 4, 5, 3, 2

8. Invagination is:
a. The infolding of cells during embryonic development (the formation of the three germ layers)
b. The attaching of one segment of the intestines to another segment
c. The infolding of cells during endocytosis and exocytosis
d. The flattening of cells during embryonic development
e. a, b, and c only

9. By week 27 of embryonic development, which of the following has already happened?
a. Gas exchange is possible
b. The heart has begun to form
c. All the vital organs have begun to form
d. Only a and b
e. a, b, and c

10. What is looping?
a. The splitting of the mesoderm
b. The forming of the atrium and ventricles
c. The beginning of the pulmonary and systemic systems
d. The forming of the five dilations in the heart
e. The tube formation of the heart

Pick THREE of the following and explain how it is involved in the development of an embryo. Be sure to mention a) the importance of each process and b) how they all tie together
1. Implantation
2. Gastrulation
3. Neurulation
4. Cephalization