What is developmental biology, and why is it important for physicians to study it? 

Developmental biology is defined as the development of a multicellular organism 

through a process of progressive change 

Give an overview of the stages of development from fertilization through maturity. 

Fertilization = union of egg and sperm 

­ Morula = embryo is proliferating in cell count but not in size 

­ Blastulation/Cleavage = creation of the trophoblast shell of cells and inner cell mass 

­ Implantation = the inner cell mass area connects to the uterine lining 

­ Gastrulation = development of three germ lines (ectoderm, mesoderm, endoderm) 

­ Neurulation = The neural plate folds into a neural tube, creating a rudimentary brain 

­ Limb development and organ development 

fertilization, morula, blastocyst, implantation 

Bilaminar disk, creation of choroid villi 

Week 5 of human prenatal development 

Review DNA structure, how genes are expressed (i.e. transcription, translation), and 

the general mechanisms for regulating gene expression.

(Slides 20, 34, 44, 55) 

­ Slide 20 is a good overview of the central dogma of biology 2 

­ Slide 34 explains transcription initiators, activators, and repressors 

­ Slide 44 explains gene expression regulation at the mRNA level 

­ Slide 55 explains gene expression regulation at the protein level 

Know the components of a signal transduction pathway, and be familiar with the 

details of the following developmental signaling pathways (at the level presented in 

lecture): Wnt, Hedgehog, FGF.

(Slides 63, then 67 through 71) 

­ These slides have good images of the Wnt and Hedgehog pathways.  I’m not sure 

about FGF though, I’ll come back for this.

Firstly, they originate in the wall of the yolk sac, in primordial germ cells 

­After they form in the sac, they migrate to the gonads through the gut 

­Recall that to replicate, germ cells must undergo meiosis 

Spermatogenesis occurs in the seminiferous tubules.  All the way 

through meiosis, in the haploid stage, sperm cells mature from a spherical cell to a long, 

narrow cell with a fully grown 9+2 dynein protein flagellum (tail) for motility (built with the 

assistance of a centriole and mitochondria).  Also, the tip of the front of sperm cells 

contain acrosomal enzymes to digest the zona pellucida of an egg upon contact 

Oogenesis, like spermatogenesis, includes meiosis and differentiation. 

However, eggs are stalled after the first of two rounds of meiosis and begin their 

differentiation there. Eggs grow monthly in follicles, which are basically soups of 

hormones and help stabilize the eggs to maturity.  The monthly occurrence of one egg 

(sometimes more, sometimes less) releasing from the ovary to the uterine tube is called 

ovulation.

­Pretesticular­ Radiation exposure, hypogonadism 

­Testicular­ Effects of mumps, genetic defect on the Y Chromosome 

­Post­testicular­ Defects of Vas Deferens/blockage 

­Impotence­ Sperm are produced, but are unable to fertilize the egg 

anovulation (can’t ovulate)  

­occluded uterine tubes 

­hostile cervical mucus 

­immunity to sperm 

Artificial insemination – 5­25% success 

In vitro fertilization ­ 20­25% success 

Gamete intrafallopian transfer (GIFT) ­ 30% success 

Intracytoplasmic sperm injection – 25% success 

released by the hypothalamus to stimulate production of LH and 

FSH in the pituitary gland of the brain 

functions according to its namesake, it stimulates follicle growth, it also 

allows release of estrogen and progesterone 

functions to stimulate meiosis round #1, ovulation, formation of the 

corpus luteum, and production of estrogen and progesterone 

a hormone produced in the ovaries that promotes proliferation 

of the endometrium, thinning of the cervical mucus, and a range of effects on other 

hormone productions 

  ­ Inhibits FSH and LH at low concentrations 

  ­Stimulates GnRH and LH at high concentrations 

­Stimulates FSH and LH at no concentration 

stimulates growth of uterine wall and associated blood 

vessels, and inhibits FSH to avoid additional follicle maturation 

The egg has sperm binding molecules 

(ZP3) that help it find the zona pellucida, or the layer that sperm must dig through to get 

to the nucleus.  The sperm does this by releasing digestive enzymes from the acrosomal 

vesicle at its tip to eat through the ZP

A wave of Ca2+ creates a barrier of glycoproteins 

at the ZP after the winning sperm enters the nucleus (most likely through the signaling 

pathway of a tyrosine kinase, protein lipase, PIP2 and IP3. 

­The egg completes its second round of meiosis as the sperm enters, their haploid 

chromosomes then join, and the first replication occurs 

­Rhythm method­ 20­30% failure 

­The pill­ hormones such as estrogen and progesterone; 1% failure 

­Depo­Provera­ Progesterone; prevents ovulation less than 1% failure. Injected 

intramuscularly and works for about 2­3 months.  

­Norplant­ subdermal hormone that lasts up to five years 

­Seasonale­ hormone allows for 4 periods per year. Taken for 91 days per pack. 

­Ortho Evra­ patch delivering hormone with less and 1% failure rate 

­Vasectomy or tubal ligation­ depends on who did your surgery 4 

­IUD (intrauterine device) ­ most popular form of birth control in the world 

­Barrier methods­ <10% 

­Male pill­ androgen inhibitor 

­Emergency contraception 

Plan B 

RU­486­ “the abortion pill” blocks progesterone

Understand human cleavage/blastulation, the formation of the 2­layered blastocyst, 

and the derivatives of the two layers

There are four features of cleavage: rotational holoblastic division, very slow, 

asynchronous, and compaction 

­ At 4.5 to 6 days, the two layers of the blastocyst form: the trophoblast, or outer cell 

mass that contributes to the placenta, and the inner cell mass, or embryoblast, that are 

considered embryonic stem cells 

­The derivative of the trophoblast is… basically not important, it’s called the 

“syncyntiotrophoblast” 

­The derivatives of the inner cell mass are… everything = the three germ layers, the 

amniotic ectoderm, and the yolk sac which creates the extraembryonic mesoderm 

There are five altogether… basically the trophoblast is connecting the embryo to the 

uterine wall and the ICM is differentiating into the epiblast and hypoblast, also the 

amniotic cavity forms and fills with fluid 

­Also, the trophoblast begins creation of the remodeled blood vessels of the embryo to 

uterus connection, which will eventually create the placenta 

Normal implantation is the phase at which the trophoblast begins to 

connect the embryo to the uterine wall.  Normally, this happens along the uterine wall. 

­Abnormal implantations usually involve an incorrect location of implantation, including 

the mesentery, the fallopian tubes, too close to the junction of uterus and cervix, and 

potentially even in the ovary 

Discuss the importance of the embryonic period (wks. 3­8) and understand why this is 

an extremely critical period of development

The embryonic period is extremely important because it is the period associated with 

the highest risk of birth defects being induced. 

­ During the embryonic period, gastrulation occurs and all major organs begin to 

develop. 

Gastrulation is the process of coordinated cell and tissue movements that rearrange 

the cells of the blastula.  During gastrulation, the three germs layers are formed 

(ectoderm, mesoderm, endoderm) 

Movements of gastrulation: 

­Invagination­ in folding of cells into embryo 

­Involution­ in turning of cell sheet over an outer layer 

­Ingression­ migration of individual cells into the embryo 

­Delamination­ 1 sheet of cells into 2 sheets 

­Epiboly­ expansion if a cell sheet over another 

Gastrulation begins on days 14­-15 of gestation at the primitive node and along the 

primitive streak 

The role of FGF (which stands for fibroblast growth factor) during gastrulation is to 

regulate cell migration and specification.  FGF is synthesized by streak cells and 

functions to down­regulate E­cadherin, which holds epiblast cells together. 

1. Ectoderm – skin and nervous system 

2. Mesoderm – skeleton, circulatory system, muscles, excretory and reproductive 

systems 

3. Endoderm – digestive and respiratory systems (Follow the path from your mouth to 

your pooper) 

The notochord begins formation on day 17 as a notochordal plate, which forms at the midline 

between the ectoderm and endoderm.  It eventually detaches from the endoderm and becomes 

the basis for the axial skeleton.  On day 18, the neural plate has surrounded the notochord.  On 

day 21, the notochord is located deep to the neural groove between two neural folds

Chordoma is a cancerous condition where tumors grow out of the ends of the notochord – near 

the clivus in the skull or near the sacrum at the bottom of the spine.  It is a clinical correlate of 

notochord defection. 

Sacrococcygeal teratoma is a cancerous condition where tumors grow out of the base of the 

coccyx/tailbone, from the remnants of the primitive streak

Caudal dysplasia is the lack of complete development/growth of the lower spine, and might be 

due to interruption in Brachyury (T) gene

Homeobox genes.  These are genes that correspond to where 

they are expressed by their location on the chromosome.  There is an example with a 

fruit fly.  There are several “Hox” homeobox derivatives

Ventral structures are promoted by BMP and FGF, dorsal 

structures are promoted by “organizer genes” (one example is noggin) in Hensen’s 

node that antagonize BMP. 

The primitive node secretes FGF8, which induces expression of 

Nodal, which cascades to up­regulate PITX­2 on the left side only.  This is due to beating 

cilia mechanically moving these factors to the left side.  Snail genes up­regulate right 

side effector genes. 

a condition in which the forebrain (telencephalon and 

diencephalon) of the embryo does not develop in two hemispheres.  It is a clinical 

correlate of neural tube differentiation (bulging)

all major visceral organs are reversed or mirrored from their normal 

locations (so, the heart is located on the right side of the thorax).  It is a clinical correlate 

of L/R axis formation 

What is Kartagener 

syndrome?

A syndrome in which all bodily cilia are immotile, and the 9+2 

formation of cilia and flagellum is distorted.

Another name for sirenomelia, which is thought to be a result of 

insufficent mesoderm due to a defect in Brachyury.  

1, to provide a barrier, 2, to exchange metabolic 

and gaseous products between maternal and fetal bloodstreams, and 3, to produce 

hormones

The maternal component of the placenta is the decidua basalis, which derives from the 

endometrium, and connects to the chorion frondosum in the uterus 

The fetal component of the placenta is the chorion frondosum, which is derived from 

the trophoblast line of cells and the extraembryonic mesoderm. 

Placental circulation is complicated.  The right and left umbilical arteries carry 

deoxygenated blood away from the fetus, and the left umbilical vein carries oxygenated 

blood to the fetus, all through the umbilical cord.  Transfer of oxygen from maternal to 

fetal blood happens in the chorion, which was created from trophoblast cells and 

extraembryonic mesoderm cells.  There is no mixing of maternal and fetal blood

The umbilical cord inserts into the fetal membrane and not the 

placenta directly, leaving blood vessels exposed and at risk for rupture

complication in which fetal blood vessels run along the external orifice of 

the uterus (the hole which we are birthed out of).  They are unsupported by the umbilical 

cord of placenta, and are at risk of rupture. 

the placenta is placed in the lower uterus, increasing the risk for 

vaginal bleeding.

the placenta separates from the uterine lining, causing much less

oxygen delivery to the fetus and much bleeding for the mother.

high blood pressure (160/110 is cutoff), large amounts of 

protein in the urine, and seizures, all during pregnancy.  It is thought to be caused 

primarily by abnormal placental placement in the uterus.   Risk factors: age history of 

preeclampsia  

Discuss twinning and how formation of the amnion/chorion in relation to the timing of 

twinning is important. 

Twinning is the description of how twins come to be, and there seem to be three 

distinctions.  From a two celled embryo… 

1. Two blasocoels can form with separate trophoblast shells, resulting in two chorions 

and two amnions in the uterus 

2. One blastocoel can form with two separated inner cell masses, resulting in one 

chorion and two amnions. 

3. One blastocoel can form with one large inner cell mass, resulting in one chorion and 

one amnion.  

*recall that chorions are areas where maternal and fetal bloods come in contact, and 

amnions are cavities in which fetuses are suspended. 

maternally derived water that increases in amount throughout the 

development of pregnancy 

A plasma protein produced by the yolk sac and liver during fetal 

development.  It is like the fetal form of albumin.  As a plasma protein, its functions are to 

maintain osmotic pressure in blood vessels and act as transporters for certain 

molecules, like heme. 

­High levels could indicate a neural tube defect 

­Low levels could indicate downs syndrome 

­High rates of error associated with the test for Alpha fetoprotein

refers to premature rupture of the amniotic sac, which would be 

considered more than one hour before birth 

Limbs or digits are entrapped in amniotic bands, which 

escape the amniotic sac due to a partial rupture and find their way to bind on to a limb or 

digit.  This syndrome often results in clubfoot.

The umbilical cord joins the amnion with the embryonic ectoderm and includes the yolk 

sac, connecting stalk, and allantois along with the umbilical blood vessels and lining 

mucus.

Umbilical circulation works by having the maternal veins and arteries connect to the

chorion, where they transfer oxygen to capillary bundles of fetal blood vessels in 

chorionic villi, which run through the umbilical cord and through the fetus.

­ Umbilical cord disorders include encircling the neck of the fetus and lacking veins or 

arteries

The neural tube is formed by the folding, convergence, and closure of the two neural 

plates at the point of the two neural crests, leaving the epidermis on top. 

The medical consequences of failure to close the neural tube are spina bifida (failure 

to close the posterior tube) and anencephaly (failure to close the anterior tube) and also 

craniorachischisis (a complete failure to close) 

­ The slides mention that folic acid consumption by pregnant and pre­pregnant women 

can prevent up to 70% of neural tube disorders, or NTDs. 

Describe the layers of the neural tube and have a general understanding of the 

molecules that regulate patterning of these layers

­ The neural tube can be organized into the forebrain, the midbrain, and the hindbrain 

which include the secondary vesicles listed in the question below. 

­ We can also consider the Shh molecule in the floor plate and the BMP4 in the roof 

plate of the neural tube, but the slides do not explain their functions. 

 ­ The SHH and BMP4 signals establish a gradient that differentiates the neuron types

Briefly describe how the brain is patterned during 

development.

How the brain is patterned 

1.  Neural tube bulges and constricts to form chambers of brain and spinal cord due to 

fluid pressure 

2.  Cell populations within neural tube rearrange to form various functioning areas of 

brain and spinal cord 

3.  Differentiation of various neurons and glia

The forebrain fails to develop in two hemispheres.  Development 

of face is compromised along with brain itself.  Various levels of severity, from barely 

noticeable phenotype difference to mental retardation to stillbirth

Overabundance of gray matter in brain development.  Characterized 

by abnormal slits or clefts in cerebral hemisphere of brain.  Bilateral slits leads to mental 

retardation and paralysis, unilateral slits lead to near average intelligence but paralysis 

of one side of body

Protrusions of the meninges, ossification defects in skull 

occur, 1 in 200,000 

Overabundance of CSF in the brain, accumulates within ventricular 

system of brain, defect is in the aqueduct of Silvius – it is obstructed and CSF is not 

properly resorbed.  Head bulges, treatment includes shunt placement in head 

The cerebellum is displaced into the foramen magnum, 

resulting in poor CSF outflow and thus hydrocephalus.  This malformation is 

characterized by any abnormality between the brain and spinal canal

Head circumference vastly below average during fetal development.  A 

number of genetic mutations cause this.  It may be present at birth or develop 

throughout the first couple years of life.  Can be associated with down’s syndrome 

The neural crest is derived from the ectoderm, forming at the dorsal end of the neural 

tube and eventually degrading and migrating to form the basis for many derivatives

The neural crest forms between the neural plate and the epidermis, there are several 

signaling molecules involved­ WNT and BMP4 

The crest migrates from the top of the neural tube down throughout the head and 

spine 

The crest derivatives include the peripheral nervous system, endocrine and 

paraendocrine structures, pigment cells, facial cartilage, bone, and connective tissue. 

­ Chordamesoderm creates the notochord 

­ Paraxial mesoderm creates somites 

­ Intermediate mesoderm makes kidneys and gonads 

­ Lateral plate mesoderm divides further into visceral mesoderm, which produces 

organs, parietal mesoderm, which creates the body wall, and space in between for the 

body cavity 

Somitogenesis occurs from the paraxial mesoderm, and somites themselves 

differentiate into sclerotome, myotome, and dermatome. 

Describe the molecular regulation of somite development, and the 

derivatives of the somites.

­ Somite development is regulated on a genetic level by Shh and Noggin factors from 

the floor of the neural tube and BMP factors from the roof of the neural tube. 

­Sclerotome(Bone and cartilage), myotome (muscle), and dermatome (dermis of skin).

 Mesenchyme­-embryonic connective tissue, somatic mesoderm, and the neural crest 

contribute to bone formation. 

The major bones of the skull are the frontal bone, two parietal bones, two temporal bones, 

occipital bone, mandible and maxilla. 

­Some bones in the skull arise from the mesenchyme while others originate from occipital 

somites and somitomeres 

­ These bones are connected along lines calls sutures, which can meet up with one another at 

soft spots called fontanelles.  Fontanelles eventually close and sutures exist only as 

demarcations of the joint of two skull bones

condition in which the coronal suture closes prematurely and 

the skull creates a point or conical structure. 

remaining supine for too long can result in the flattening of one side of 

the head 

the head is very wide but the back of the head is flat, due to early 

closure of coronal and landoinal sutures

­Vertebrae form from the sclerotome portions of the somites, which are derived from paraxial 

mesoderm 

­Sclerotome cells migrate around the spinal cord and notochord to merge with cells from the 

opposing somite on the other side of the neural tube 

­Notochord forms part of the intervertebral disks 

­Each vertebra is formed from the combination of the caudal half of one somite and the cranial 

half of its neighbor 

­Regulated by Hox genes 

Limb development occurs between 5 and 8 weeks of gestation.  The lateral plate 

mesoderm and the ectoderm partner up to create a limb bud.  FGF8 and FGF10 induce 

the ectoderm to perform steady mitosis in the “progress zone” which slowly builds the 

limb from the limb bud. 

­Differential genes in the mesoderm have homeoboxes that control for the bones of 

each limb to grow in the correct spots, while the ectoderm just grows around the limb. 

Mutation of homeobox genes can result in defects like synpolydactyly, or the 

joining of fingers. 

­ Being born without a limb, aka Meromeila or Amelia 

­ Clubfoot (inversion of feet at the ankles) 

­ Cleft hand or cleft foot (missing fingers or toes) 

­ Digit defects like brachydactyly (fingers shorter), syndactyly (fingers stuck together) , 

polydactyly (extra fingers), ectrodactyly (missing fingers) 

defective connective tissue, implications on the heart and blood 

vessels… apparently you are really tall and have a stretched out skeleton 

Stunted growth due to defective thyroid glands/hormones 

Malfunctioning osteoclasts create bones that are extremely dense, so 

it is kind of like the opposite of osteoporosis

The lateral body folds allow the amnion to surround the embryo and also close the gut 

hole

The cranial and caudal body folds create our head and tail and create a duct between 

our embryo and the yolk sac (called the vitelline duct) 

­ There are ventral body fold defects including ectopia cordis (heart located outside of 

the thorax), gastroschisis, and bladder and cloacal exstrophy. 

­ Also, the neural tube folds in on itself, and failure to do that results in spina bifida or 

anencephaly.