DEVELOPMENT

• Sexual reproduction is the process by which organisms produce

offspring by making sex cells called gametes.
• Male gametes are called sperm (spermatozoa) and female gametes
are called secondary oocytes.
• The organs that produce gametes are called gonads; these are the
testes in the male and the ovaries in the female.
• The details of sperm formation in the testes and secondary oocyte
formation in the ovaries
• Once sperm have been deposited in the female reproductive tract and
a secondary oocyte has been released from the ovary, fertilization can
occur.
• This process initiates a cascade of developmental events that, when
completed properly, produces a healthy newborn baby.
• Pregnancy- is a sequence of events that begins with fertilization,
proceeds to implantation, embryonic development, and fetal
development, and ideally ends with birth about 38 weeks later, or 40
weeks after the mother’s last menstrual period.
• 0-8 WEEKS- EMBRYO
• 8 WEEKS TO BIRTH- FETUS
 Developmental biology
• Developmental biology is the study of the sequence of events from
the fertilization of a secondary oocyte by a sperm cell to the
formation of an adult organism.
• From fertilization through the eighth week of development-the
embryonic period
• Developing human is called an embryo.
• Embryology- is the study of development from the fertilized egg
through the eighth week.
• The fetal period begins at week nine and continues until birth. During
this time, the developing human is called a fetus
• Prenatal development- is the time from fertilization to birth
and includes both the embryonic and fetal periods.
• Prenatal development is divided into periods of three
calendar months each, called trimesters.
First Trimester- the most critical stage of development, all of
the major organ systems begin to form. Because of the
extensive, widespread activity, it is also the period when the
developing organism is most vulnerable to the effects of
drugs, radiation, and microbes.
• Second Trimester- is characterized by the nearly
complete development of organ systems. By the end
of this stage, the fetus assumes distinctively human
features.
• Third Trimester -represents a period of rapid fetal
growth in which the weight of the fetus doubles.
During the early stages of this period, most of the
organ systems become fully functional.
• Female reproductive organs involved in the major events of the
embryonic and fetal periods are the ovaries, uterine tubes, uterus,
and vagina.
• The ovaries are paired organs in the superior portion of the pelvic
cavity on either side of the uterus.
• During the reproductive years of a female, they produce secondary
oocytes and discharge them into the peritoneal cavity each month, a
process called ovulation.
• Each of the two uterine (fallopian) tubes, which extend laterally from the
uterus, provides an exit route from the peritoneal cavity for the secondary
oocyte. In the uterine tubes, a secondary oocyte can come in contact with
sperm, and the tubes can transport a fertilized (or unfertilized) oocyte to the
uterus.
• The uterus- an inverted pear-shaped organ in the pelvic and lower abdominal
cavity, consists of a superior portion (fundus), middle portion (body), and
inferior portion (cervix). The interior of the body of the uterus is called the
uterine cavity, and the interior of the cervix is known as the cervical canal.
• After puberty, in preparation for implantation of the fertilized ovum, the uterus
forms a vascular, glandular lining called the endometrium during each
menstrual cycle. Part of the endometrium is shed during menstruation.
• Deep to the endometrium is a muscular layer called the myometrium.
• The largest mass of smooth muscle in the human body, the myometrium
is responsible for the strong contractions that expel the endometrium
during menstruation and help push the fetus out of the uterus during
labor.
• The uterus serves as the site of implantation of a fertilized ovum and
development of the fetus during pregnancy.
• The cervix of the uterus connects to the vagina, a multipurpose canal
that opens to the exterior.
• The vagina serves as the receptacle for the penis during sexual
intercourse, the outlet for menstrual flow, and the passageway for
childbirth.
 First Week of Development
• The first week of development;
• Is characterized by several significant events including
Fertilization
Cleavage of the zygote
Blastocyst formation
Implantation
 Fertilization
• During fertilization the genetic material from a haploid sperm cell and a haploid
secondary oocyte merges into a single diploid nucleus.
• Of the approximately 200 million sperm introduced into the vagina, fewer than 2
million (1 percent) reach the cervix and only about 200 (0.0001 percent) reach
the secondary oocyte
• Fertilization normally occurs in the uterine (fallopian) tube within 12 to 24 hours
after ovulation- ampular region
• Sperm can remain viable for about 48 hours, although a secondary oocyte is
viable for only about 24 hours after release from the ovary.
• Pregnancy is most likely to occur if intercourse takes place during a 3-day window
— from 2 days before ovulation to 1 day after ovulation.
Fertilization……cont……
• Sperm swim from the vagina into the cervical canal propelled by the whiplike
movements of their tails (flagella).
• The passage of sperm through the rest of the uterus and into the uterine tube results
mainly from contractions of the walls of these organs.
• Sperm that reach the vicinity of the oocyte within minutes after ejaculation are not
capable of fertilizing it until about seven hours later.
• During this time in the female reproductive tract, mostly in the uterine tube, sperm
undergo capacitation- a series of functional changes that cause the sperm’s tail to
beat even more vigorously and prepare its plasma membrane to fuse with the
oocyte’s plasma membrane.
• During capacitation, secretions in the female reproductive tract remove cholesterol,
glycoproteins, and proteins from the plasma membrane around the head of the
sperm cell.
• Only capacitated sperm are capable of being attracted by and responding to chemical
factors produced by the surrounding cells of the ovulated oocyte
• For fertilization to occur, a sperm cell first must penetrate the
• Corona Radiata the cells that surround the secondary oocyte
• Zona Pellucida- the clear glycoprotein layer between the corona radiata and
the oocyte’s plasma membrane.
• The acrosome, a helmetlike structure that covers the head of a sperm,
contains several enzymes
• Enzymes and strong tail movements by the sperm help it penetrate the cells of
the corona radiata and come in contact with the zona pellucida.
• One of the glycoproteins in the zona pellucida acts as a sperm receptor,
binding to specific membrane proteins on the acrosome to trigger the
acrosomal reaction, the release of the contents of the acrosome.
• The acrosomal enzymes digest a path through the zona
pellucida as the lashing sperm tail pushes the sperm cell
onward.
• Although many sperm undergo acrosomal reactions, only the
first sperm cell to penetrate the entire zona pellucida and
reach the oocyte’s plasma membrane undergoes syngamy,
fusion with the oocyte.
• This results in a reaction within the oocyte that makes the
zona pellucida impermeable, blocking polyspermy, fertilization
by more than one sperm cell.
• Once a sperm cell enters a secondary oocyte, the oocyte completes
meiosis II.
• It divides into a larger ovum (mature egg) and a smaller second polar
body, which contains DNA but no cytoplasm. The polar body
eventually fragments and disintegrates.
• The nucleus in the head of the sperm develops into the male
pronucleus, and the nucleus in the fertilized ovum develops into the
female pronucleus.
• After the pronuclei form, they fuse, producing a single nucleus with
23 chromosomes from each pronucleus.
• Fusion of the two haploid (n) pronuclei restores the diploid number
(2n) of 46 chromosomes in the fertilized ovum, now called a zygote.
• Fertilization takes approximately 24 hours.
• Dizygotic (fraternal) twins are produced from the independent release of two
secondary oocytes and the subsequent fertilization of each of them by different
sperm. They are the same age and in the uterus at the same time, but genetically
they are as dissimilar as any other siblings. Dizygotic twins may or may not be
the same sex.
• Because monozygotic (identical) twins develop from a single fertilized ovum,
they contain exactly the same genetic material and are always the same sex, but
the expression of that genetic information may differ.
• Monozygotic twins arise from separation of the developing zygote into two
embryos; 99 percent of the time this occurs within 8 days of fertilization.
• Separations that occur later than 8 days are likely to produce conjoined twins, a
situation in which the twins are joined together and share some body structures.
• The surgical separation of conjoined twins is a very delicate and risky procedure.
Mortality rates for the procedure depend on the type of connection and the
organs shared.
 Cleavage of the Zygote
• After fertilization, the zygote undergoes mitotic cell divisions called cleavage that
initially increase the number of cells without increasing the overall size of the cell
mass.
• The first division of the zygote begins about 24 hours after fertilization and is
completed about 6 hours later.
• Each succeeding division takes slightly less time. By the second day after
fertilization, the second cleavage is completed and there are four cells
• By the end of the third day, there are 16 cells.
• The progressively smaller cells produced by cleavage are called blastomeres.
• Successive cleavages eventually become more rapid and produce a solid sphere
of cells called the morula.
• The morula is still surrounded by the zona pellucida and is about the same size as
the original zygote.
Blastocyst Formation
• Fourth day- the number of cells in the morula increases as it
continues to move through the uterine tube toward the uterine
cavity.
• Morula enters the uterine cavity on day 4 or 5, a glycogen-rich
secretion from the glands of the endometrium passes into the uterine
cavity and enters the morula through the zona pellucida.
• This secretion, called uterine milk, along with nutrients stored in the
cytoplasm of the blastomeres of the morula, provides nourishment
for the developing morula.
• 32-cell stage- the fluid enters the morula, collects between the
blastomeres, and reorganizes them around a large fluid-filled cavity
called the blastocyst cavity
• Once the blastocyst cavity is formed, the developing mass is referred
to as the blastocyst.
• Though it now has hundreds of cells, the blastocyst is still about the
same size as the original zygote
• During the formation of the blastocyst, two distinct cell populations
arise: the embryoblast and trophoblast.
• The embryoblast, or inner cell mass, is located internally and
eventually develops into the embryo and some of the extraembryonic
membranes
• The trophoblast is the outer superficial layer of cells that forms the
sphere-like wall of the blastocyst.
• It will ultimately develop into the outer chorionic sac that surrounds the
fetus and the fetal portion of the placenta, the site of exchange of
nutrients and wastes between the mother and fetus.
• On about the fifth day after fertilization, the blastocyst is released from
the zona pellucida by digesting a hole in it with an enzyme, and then
squeezing through the hole.
• This shedding of the zona pellucida is necessary in order to permit the
next step, implantation (attachment) into the vascular, glandular
endometrial lining of the uterus.
End
 Third Week of Development
• The third embryonic week begins a six-week period of rapid
development and differentiation.
• During the third week, the three primary germ layers are established,
which lays the groundwork for organ development in weeks four
through eight.
 Gastrulation
• The first major event of the third week of development, gastrulation,
occurs about 15 days after fertilization
• In this process, the bilaminar (two-layered) embryonic disc,
consisting of epiblast and hypoblast, is transformed into a trilaminar
(three-layered) embryonic disc consisting of three primary germ
layers: the ectoderm, mesoderm, and endoderm
• The primary germ layers are the major embryonic tissues from which
the various tissues and organs of the body develop
Gastrulation…….
• Gastrulation involves well-coordinated and important rearrangement
and migration of cells from the epiblast to set the stage for the
important interactions of the newly positioned cells
• The first evidence of gastrulation is the formation of the primitive
streak-a faint groove on the dorsal surface of the epiblast that
elongates from the posterior to the anterior part of the embryo
• The primitive streak clearly establishes the head and tail ends of the
embryo, as well as its right and left sides
• At the head end of the primitive streak a small group of epiblast cells
forms a rounded structure called the primitive node
• Following formation of the primitive streak, cells of the epiblast move inward
and detach from the primitive streak to form the mesoblast.
• Once the cells of the mesoblast begin to migrate beneath the overlying epiblast,
some of them displace the original hypoblast by pushing it laterally and
completely replace it with a new layer of cells.
• This new layer of cells forming the roof of the yolk sac is the endoderm (endo-
=inside; -derm=skin)
• Other migrating mesoblast cells remain between the epiblast and newly formed
endoderm to form a new layer, the mesoderm (meso-=middle).
• Cell placement and differentiation of cells within this layer are crucial to inducing
further development of the final body plan.
• Cells remaining in the epiblast then form the ectoderm (ecto-=outside)
Fates of Primary Germ Layers
• 16 days after fertilization, mesodermal cells from the primitive node migrate
toward the head end of the embryo and form a hollow tube of cells in the midline
called the notochordal process.
• By days 22–24, the notochordal process becomes a solid cylinder of cells called
the notochord
• This structure plays an extremely important role in induction -a process in which
one tissue (inducing tissue) stimulates the specialization of an adjacent tissue
(responding tissue)
• An inducing tissue usually produces a chemical substance that influences the
responding tissue
• The notochord induces certain neighboring mesodermal cells to develop into
parts of vertebrae (back bones), induces the overlying ectoderm to fold inward to
form the nervous system, and contributes to the formation of intervertebral discs
between vertebrae
• Also during the third week of development, two faint depressions
appear on the dorsal surface of the embryo where the ectoderm and
endoderm make contact but lack mesoderm between them
• The structure closer to the head end is called the oropharyngeal
membrane
• It breaks down during the fourth week to connect the mouth cavity to
the pharynx (throat) and the remainder of the gastrointestinal tract.
• The structure closer to the tail end, called the cloacal membrane
(sewer), degenerates in the seventh week to form the openings of the
anus and urinary and reproductive tracts.
• When the cloacal membrane appears, the wall of the yolk sac forms a
small vascularized outpouching called the allantois (allant-=sausage)
that extends into the connecting stalk.
• In nonmammalian organisms enclosed in an amnion (reptiles and
birds), the allantois is used for gas exchange and waste removal.
• Because the mammalian placenta performs these functions, the
allantois is not a prominent structure in most mammals.
• Nevertheless, it does function in early formation of blood and blood
vessels and it is associated with the development of the urinary
bladder.
Fate Map of cells Established During
Gastrulation
• Cells of the epiblast that migrate and ingress through the primitive streak
have been mapped and their ultimate fates determined as follows:-
1. Cells that ingress through the cranial region of the node become notochord;
2. Cells migrating at the lateral edges of the node and from the cranial end of
the streak become paraxialmesoderm;
3. those migrating through the mid-streak region become intermediate
mesoderm;
4. those migrating through the more caudal part of the streak form lateral
plate mesoderm;
5. cells migrating caudal-most part of the streak contribute to extraembryonic
mesoderm (the other source of this tissue is the primitive yolk sac
[hypoblast]
 Neurulation
• In addition to inducing
mesodermal cells to develop
into parts of vertebrae, the
notochord also induces
ectodermal cells above it to form
the neural plate.
• By the end of the third week the
neural plate begins the process
of invagination, an infolding of
the ectoderm neural plate cells
into the underlying mesoderm.
• During this process, the lateral edges of the neural plate become
pressed region or groove between the neural folds is called the neural
groove
• As the fold deepens, the neural folds approach each other and fuse,
closing the neural groove and converting the neural plate into a
neural tube that is pushed beneath the surface ectoderm into the
underlying mesoderm
• Neural tube cells then develop into the brain and spinal cord.
• The process of formation of the neural plate, neural folds, and neural
tube is called neurulation.
• As the neural tube forms, some of the ectodermal cells migrate
dorsolaterally to form several layers of cells called the neural crest.
• This population of cells is more extensive in the head end of the
embryo where it forms a large mass of cells dorsolateral to the neural
tube
• Neural crest cells form all the sensory neurons and postganglionic
motor neurons of the peripheral nerves, adrenal medullae,
melanocytes (pigment cells) of the skin, the arachnoid mater and pia
mater of the brain and spinal cord, and almost all of the skeletal and
connective tissue components of the head.
• Approximately four weeks after fertilization, the head end of the neural tube
develops into three enlarged areas called primary brain vesicles
 Development of Somites
• By about the 17th day after fertilization, the mesoderm adjacent to the
notochord and neural tube forms paired longitudinal columns of
paraxial mesoderm.
• The mesoderm lateral to the paraxial mesoderm forms paired
cylindrical masses called intermediate mesoderm.
• The mesoderm lateral to the intermediate mesoderm consists of a
pair of flattened sheets called lateral plate mesoderm.
• The paraxial mesoderm soon segments into a series of paired,
cubeshaped structures called somites (little bodies).
• By the end of the fifth week, 42–44 pairs of somites are present.
• The number of somites that develop over a given period can be
correlated to the approximate age of the embryo.
• Each somite differentiates into three regions: a myotome, a
dermatome, and a sclerotome
• The myotomes develop into the skeletal muscles of the neck, trunk,
and limbs; the dermatomes form connective tissue, including the
dermis of the skin; and the sclerotomes give rise to the vertebrae and
ribs
Development of the Intraembryonic
Coelom
• In the 3rd of development, small spaces appear in the lateral plate mesoderm.
These spaces soon merge to form a larger cavity called the intraembryonic coelom.
• This cavity splits the lateral plate mesoderm into two parts called the splanchnic
mesoderm and somatic mesoderm
Splanchnic mesoderm (visceral), which is adjacent to the endoderm and yolk sac,
forms the heart and the visceral layer of the serous pericardium, blood vessels, the
smooth muscle and connective tissues of the respiratory and digestive organs, and
the visceral layer of the serous membrane of the pleurae and peritoneum
Somatic mesoderm (body), which is adjacent to the ectoderm and amnion, gives
rise to the bones, ligaments, blood vessels, and connective tissue of the limbs and
the parietal layer of the serous membrane of the pericardium, pleurae, and
peritoneum
• During the second month of development, the intraembryonic coelom is
partitioned into the pericardial, pleural, and peritoneal cavities.
Development of the Cardiovascular
System
• At the beginning of the third week, angiogenesis, the formation of
blood vessels, begins in the extraembryonic mesoderm of the yolk
sac, connecting stalk, and chorion.
• This early development is necessary because there is insufficient yolk
in the yolk sac and ovum to provide adequate nutrition for the rapidly
developing embryo
• Angiogenesis is initiated when mesodermal cells differentiate into
hemangioblasts
• These then develop into cells called angioblasts, which aggregate to
form isolated masses of cells referred to as blood islands
• As the blood islands throughout the embryonic mesoderm grow they
fuse together, forming an extensive system of blood vessels within the
embryo
• About 3 weeks after fertilization, blood cells and blood plasma begin
to develop outside the embryo—in the walls of the yolk sac, allantois,
and chorion—from hemangioblasts in blood vessels.
• These then develop into pluripotent stem cells that form blood cells.
• Blood formation begins within the embryo at about the fifth week in the liver
and around the twelfth week in the spleen, red bone marrow, and thymus.
• The heart forms from splanchnic mesoderm in the head end of the embryo
on day 18 or 19 after fertilization. This region of mesodermal cells is called
the cardiogenic area
• In response to induction signals from the underlying endoderm, these
mesodermal cells ultimately form a pair of endocardial tubes
• The tubes then fuse to form a single primitive heart tube.
• By the end of the third week, the primitive heart tube bends on itself,
becomes S-shaped, and begins to beat. It then joins blood vessels in other
parts of the embryo, connecting stalk, chorion, and yolk sac to form a
End of CAT
 Development of the Chorionic
Villi and Placenta
• As the embryonic tissue invades the uterine wall, maternal uterine vessels
are eroded and maternal blood fills spaces, called lacunae, within the
invading tissue.
• By the end of the second week of development, chorionic villi begin to
develop.
• These fingerlike projections consist of chorion (syncytiotrophoblast
surrounded by cytotrophoblast) that project into the endometrial wall of
the uterus.
• By the end of the third week, blood capillaries develop in the chorionic villi
• Blood vessels in the chorionic villi connect to the embryonic heart by way
of the umbilical arteries and umbilical vein through the connecting (body)
stalk, which will eventually become the umbilical cord
• The fetal blood capillaries within the chorionic villi project into the
lacunae, which unite to form the intervillous spaces where the
chorionic villi (and the fetal blood vessels within them) are bathed in
maternal blood.
• However maternal blood and fetal blood do not mix directly.
• Instead, oxygen and nutrients in the mother’s blood diffuse from the
intervillous spaces across the plasma membranes of the chorion and
the capillaries of the villi.
• Waste products such as carbon dioxide diffuse in the opposite
direction
 Fourth Week of Development
• The fourth through eighth weeks are very significant in embryonic
development because all major organs appear during this time.
• The term organogenesis refers to the formation of body organs and
systems
• By the end of the eighth week, all major body systems have begun to
develop, although their functions for the most part are minimal
• Organogenesis requires the presence of blood vessels to supply
developing organs with oxygen and other nutrients.
• The endothelial cells of blood vessels apparently provide some type of
developmental signal, either a secreted substance or a direct cell-to-
cell interaction, that is necessary for organogenesis
 During the fourth week of development……….
EMBRYONIC FOLDING
• During the fourth week of development, the embryo undergoes
dramatic changes in shape and nearly triples its size.
• Converted from a flat, two-dimensional trilaminar embryonic disc to a
three-dimensional cylinder, via a process called embryonic folding
• The cylinder consists of endoderm in the center (gut lining),
ectoderm primarily on the outside (epidermis), and mesoderm in
between.
• The cylinder does contain some internal ectoderm from neurulation
(the nervous system and most of the structures of the head)
• The main force responsible for embryonic folding is the different rates
of growth of various parts of the embryo, especially the rapid
longitudinal growth of the nervous system (neural tube)
• Folding in the median plane produces a head fold and a tail fold, while
folding in the horizontal plane results in the two lateral folds
• As a result of the folding, the embryo curves into a C-shap
• Head fold brings the developing heart and mouth into their eventual
adult positions
• The tail fold brings the developing anus into its eventual adult
position
• The lateral folds form as the lateral margins of the trilaminar
embryonic disc bend ventrally, curving toward the open part of the C.
• As they move toward the midline, the lateral folds incorporate the
dorsal part of the yolk sac into the embryo as the primitive gut, the
forerunner of the gastrointestinal tract
• The primitive gut differentiates into an anterior foregut, an
intermediate midgut, and a posterior hindgut
• Oropharyngeal membrane is located in the head end of the embryo. It
separates the future pharyngeal (throat) region of the foregut from
the stomodeum (stomo-=mouth), the future oral (mouth) cavity
• Because of head folding, the oropharyngeal membrane moves
downward and the foregut and stomodeum move closer to their final
positions
• When the oropharyngeal membrane ruptures during the fourth week,
the pharyngeal region of the pharynx and stomodeum are brought
into contact with each other
• In a developing embryo, the last part of the hindgut expands into a cavity
called the cloaca
• On the outside of an embryo is a small cavity in the tail region called the
proctodeum (procto-=anus)
• The cloacal membrane separates the cloaca from the proctodeum
• During embryonic development, the cloaca divides into a ventral urogenital
sinus and a dorsal anorectal canal
• As a result of tail folding, the cloacal membrane moves downward and the
urogenital sinus, anorectal canal, and proctodeum move closer to their final
positions
• When the cloacal membrane ruptures during the seventh week of
development, the urogenital and anal openings are created
• Embryonic folding, development of somites, and development of the
neural tube, four pairs of pharyngeal arches or branchial arches
(branch=gill) begin to develop on each side of the future head and
neck regions during the fourth week.
• These four paired structures begin their development on the twenty-
second day after fertilization and form swellings on the surface of the
embryo.
• Each pharyngeal arch consists of an outer covering of ectoderm and
an inner covering of endoderm, with mesoderm in between
• Each pharyngeal arch has-artery, a cranial nerve, cartilaginous skeletal
rods that support the arch, and skeletal muscle tissue that attaches to
and moves the cartilage rods
• On the ectodermal surface of the pharyngeal region, each pharyngeal
arch is separated by a groove called a pharyngeal cleft
• The pharyngeal clefts meet corresponding balloonlike outgrowths of the
endodermal pharyngeal lining called pharyngeal (branchial) pouches
• Where the pharyngeal cleft and pouch meet to separate the arches, the
outer ectoderm of the cleft contacts the inner endoderm of the pouch
and there is no mesoderm between
• Each pharyngeal arch is a developmental unit and includes a skeletal
component, muscles, a distinct cranial nerve, and blood vessels
• human embryo has four pharyngeal arches
• Each of these arches develops into a specific and unique component
of the head and neck region
• The first pharyngeal arch is often called the mandibular arch because
it forms the jaws (the mandible is the lower jawbone)
• The first sign of a developing ear is a thickened area of ectoderm, the
otic placode (future internal ear), distinguished about 22 days after
fertilization
• A thickened area of ectoderm called the lens placode, which will
become the eye, appears at this time 22nd day
• Middle of the fourth week, the upper limbs begin their development
as ectoderm-covered outgrowths called upper limb buds.
• By the end of the fourth week, the lower limb buds develop.
• The heart also forms a distinct projection on the ventral surface of the
embryo called the heart prominence, just caudal to the pharyngeal
arches, and a tail becomes visible
Fifth Through Eighth Weeks of
Development
• Fifth week of development-growth of the head is
considerable because of very rapid development of the brain
• End of the 6th week
The head has grown even larger relative to the trunk, and
the limbs show substantial development
In addition, the neck and trunk begin to straighten, and the
heart is now four-chambered
• Seventh week- the various regions of the limbs become
distinct and the beginnings of digits appear
• Start of the eighth week-
The final week of the embryonic period, the digits of the
hands are short and webbed and the tail is still visible, but
shorter
The eyes are open and the auricles of the ears are visible.
• End of the eighth week-
All regions of limbs are apparent; the digits are distinct and no
longer webbed due to removal of cells via apoptosis.
Eyelids come together and may fuse, the tail shortens and
becomes imperceptible, and the external genitals begin to
differentiate
The embryo now has clearly human characteristics.