Embryogensis

Question 1

Human Development Timeline

Answer 1

• weeks 1-8 of human pregnancy are embryogenesis (sometimes called organogenesis) when organ primordia (organs in their earliest recognizable stage of development) are established
• the embryonic period is followed by the fetal period of continued differentiation and growth

Question 2

Ovulation to implantation

Answer 2

• oocyte is fertilized in the ampullar region of the uterine tube
• the zygote then undergoes cleavage divisions to form a morula and then a blastocyte
• by the end of the first week, the blastocyst begins implantation into the uterine wall

Question 3

Fertilization

Answer 3

• male sperm and female oocyte gametes fuse
• sperm are viable for several days in the female reproductive tract are moved to the uterine tube via muscular contractions of the uterus and uterine tube towards the ovary. This trip can be 30 minutes or 6 days
• after gamete fusion the male and female pronuclei (both hapliod) replicate their DNA and the maternal and paternal chromosomes organize for mitotic division
• the duplicated chromosome sets split to provide each cell of the two cell zygote the normal diploid number of chromosome
• fertilization results in the formation of a diploid zygote and activates cleavage divisions (without fertilization, the oocyte degenerates 24 hours after ovulation

Question 4

Cleavage Divisions

Answer 4

• once the zygote has reached the two-cell stage, it has cleavage mitotic divisions
• these reduce the size of cells and increase the number of cells
• during these stages, the cells are known as blastomeres
• after the third cleavage, blastomeres maximize their contact with each other and form a compact ball of cells
• this process of compaction segregates inner cells from outer cells.
• about 3 days after fertilization the compacted embryo divids to form a 16- cell morula (mulberry)

Question 5

Cell stage and timing

Answer 5

2 cell- about 30 hours post fetilization
4 cell- about 40 hours
16 cells- 3 days
Late morula stage- 4 days

Question 6

Blastocyst formation

Answer 6

• inner cells of the morula constitute the inner cell mass
• the inner cell mass gives rise to tissues in the embryo proper and the outer cells give rise to the trophoblast that later contributes to the placenta
• Fluid then penetrates into the intracellular spaces of the ICM to form a blastocoel
• at the time the embryo is a blastocyst
• the outer cells flatten and form the wall of the blastocyst

Question 7

Embryonic Stem Cells

Answer 7

• derived from the inner cell mass (ICM) of the embryo
• these cells are pluripotent (can give rise to all of the cell types of the body)
• ES cells have potential to treat a variety of disease such as diabetes, Alzheimer’s and Parkinson’s diseases
• however ES cells pose ethical issues since these cells are harvested from a viable embryo
• induced pluripotent stem cells are alternative stem cells that are generated from adult cells

Question 8

Trophoblast cells

Answer 8

• 7 days
• trophoblast cells penetrate between the epithelial cells of the uterine mucosa (endometrium)
• recent studies suggest molecules called L-selectins (carbohydrate binding proteins) on trophoblast cells interact with carbohydrate receptors on the uterine epithelium to mediate attachment of the blastocyst to the uterus

Question 9

Day 8

Answer 9

• the blastocyst is partially embedded in the endometrium and the trophoblast differentiates into two layers
• 1) cytotrophoblast- an inner layer of mononucleated cells and
  2) syncytiotrophoblast- an outer multinucleated layer that lacks distinct cell boundaries. The syncytiotrophoblast continues to expand into the uterine wall

Question 10

Day 9

Answer 10

• the cells of the inner cell mass differentiate into two layers
  1) hypoblast and 2) epiblast
• together these layers form a flat bilaminar disc
• the amniotic cavity forms within the epiblast
• the trophoblast invades maternal capillaries to establish uteroplacental circulation

Question 11

Origin of embryonic tissues

Answer 11

• the epiblast layer gives rise to all tissues in the embryo proper (embryonic ectoderm, endoderm, mesoderm)
• the hypoblast layer and trophoblast contribute to extraembryonic tissues

Question 12

Ectopic Pregnancy

Answer 12

• abnormal implantation
• normally the blastocyst implants along the anterior or posterior wall of the uterus
• occasionally implantation occurs near the cervix or outside the uterus
• occurs in 2% of all pregnancies, and account for 9% of all pregnancy-related maternal deaths
• Tubal 95% (mostly ampullary)
• Ovarian 3%
• Cesarean scar 1%
• Cervical 1%
• Abdominal 1%

Question 13

Goals of gastrulation

Answer 13

1) Bring inside the embryo areas destined to form endodermal organs
2) Surround the embryo with cells capable of forming ectoderm
3) Place mesodermal cells in proper positions in between

Question 14

Process of gastrulation

Answer 14

• in the third week of development the process of gastrulation establishes three germ layers (ectoderm, mesoderm, and endoderm) that will give rise to specific tissues in the embryo
• gastrulation begins with the formation of the primitive streak on the surface of the epiblast
• the primitive streak becomes a narrow groove with a structure called the primitive node surrounding a primitive pit at the cephalic end

Question 15

Invagination

Answer 15

• next epiblast cells migrate toward the primitive streak and then detach from the epiblast and move through the the streak to slip beneath it
• the inward movement is the invagination

Question 16

Development to endoderm and mesoderm

Answer 16

• once cells have invaginated some displace the hypoblast to create the endoderm
• other invaginating cells lie between the epiblast and the new endoderm to form the mesoderm layer
• cells remaining in the epiblast form the ectoderm
• the epiblast, through the process of gastrulation, is the source of all germ layers that give rise to all tissues in the embryo

Question 17

Three germ layers give rise to embryonic tissues

Answer 17

• the primary germ layers (endoderm, mesoderm and ectoderm) are formed and organized in their proper locations as a result of gastrulation
• endoderm, the most internal germ layer, forms the lining of the gut and other internal organs
• ectoderm, the most exterior germ layer forms skin, brain, the nervous system, and other external tissues
• mesoderm, the middle germ layer forms the skeletal system, and the circulatory system

Question 18

Overview of neurulation

Answer 18

• the process by which the neural plate forms the neural tube
• induction of the neural plate with signaling with BMP, Wnt, FGF, RA

Question 19

Steps of Neurulation

Answer 19

1) formation and folding of the neural plate
2) elevation of the neural crest
3) convergence of the neural folds
4) closed of the neural tube when the neural folds are brought in contact with one another
- neural crest cells migrate away to contribute to several tissues, which leaves the neural tube separate from the epidermis

Question 20

Neurulation divides neural ectoderm

Answer 20

• the events of neurulation divide the ectoderm into three major domains:
  1) the internally positioned neural tube, which will form the brain and spinal cord
  2) externally positioned surface ectoderm that will primarily from skin (epidermis)
  3) the neural crest cells that migrate to new locations to give rise to many cell types

Question 21

Neural tube closure

Answer 21

• in humans there are 3 sites
• at each of the sites, fusion of the neural folds proceeds bidirectionally
• until fusion is complete, the cephalic and caudle ends of the neural tube communicate with the amniotic cavity via anterior and posterior neuropores
• failure of close in different regions of the neural tube results in different types of neural tube defects
• failure to close the posterior neuropore results in spina bifida which can vary in severity
• failure to close at the other 2 sites results in an open anterior neuropore and a lethal condition called anacephaly in which the forebrain remains in contact with amnionic fluid and degenerates
• complete failure of closure along the entire neural tube results in craniorachischisis
• human neural tube close depends on interplay between genes and environment. Several genes (Pax3, Shh) are essential for neural tube closure, but dietary factors such as cholesterol and folate are also important

Question 22

Folic Acid

Answer 22

• it is estimated that 50-70% of neural tube defects can be prevented if women take 400 micrograms of folic acid daily beginning at 3 months prior to conception and continuing throughout pregnancy
• folate is a generic term for water soluble, B vitamin that serves as an essential coenzyme in single-carbon transfers in the metabolism of nucleic and amino acids and thus fills an important function in purine and pyrimidine metabolism
• it occurs in certain natural foods as polyglutamate, a form less absorbed that free folate
• folic acid (a monoglutamic acid) is the oxidized and most active form of the vitamin, found rarely in food it is the form used in vitamin preparations and food fortification

Question 23

Neural Crest cells

Answer 23

• the neural crest cells arising in the ectoderm at the margins of the neural tube
• these cells migrate to many different locations and differentiate into many cell types within the embryo
• this means that many different systems (neural, skin, teeth, head, face, heart, endocrine, GI tract) will also have a contribution from the neural crest cells
• NCCs undergo a epithelial-to-mesenchymal (loosely organized connective tissue) transition at the dorsal neural tube and then migrate to give rise to tissues.

Question 24

Neural crest cells by region

Answer 24

• along the anterior-posterior body axis, NCCs migrate to different tissues and form different cell types
• the NCC can be divided into four main (but overlapping) anatomical regions with characteristic derivatives
  1) Cranial (cephalic)- produce craniofacial cartilage, bone, neurons, glia and connective tissue. These cells also enter pharyngeal arches to give rise to thymic cells, teeth and bones of the middle ear and jaw
  2) Cardiac- a subregion of the cranial NCC that develops into melanocytes, neurons, cartilage and connective tissue. Also produces the muscular-connective tissue wall and septum of the cardiac outflow tract that gives rise to the large arteries (aorta and pulmonary artery)
  3) Trunk NCC- migrates to form dorsal root ganglia containing sensory neurons or sympathetic ganglia and the adrenal medulla
  4) Enteric (vagal and sacral) NCC- form the parasympathetic ganglia of the gut

Question 25

Migration patterns of NCCs

Answer 25

• NCCs are a migratory cell population that give rise to the majority of cartilage, bone, CT, and sensory ganglia of head
• NCCs contribute to the frontonasal process, the mesenchyme surrounding the optic placode, and the maxillary and mandibular prominences of the the first brachial arch as well as the more caudal branchial arches

Question 26

Cardiac NCCs

Answer 26

• cardiac NCCs enter the outflow of the heart to gernate the septum between the great arteries
• NCCs migrate to pharyngeal arches 3,4 and 6 and enter the truncus arteriosis (cardiac outflow tract) to generate the septum