HISTOLOGY

1B Dr. NOELYN BERNAL

H-03 THE NUCLEUS

TOPIC OUTLINE

I. The Nucleus
a. Components of the Nucleus
A.1. Nuclear Envelope
A.2. Chromatin COMPONENTS OF THE NUCLEUS
A.3. Nucleolus
b. Cell Cycle
A.1 NUCLEAR ENVELOPE
c. Stem Cells and Tissue Renewal
d. Meiosis
e. Apoptosis - forms a selectively permeable barrier
between the nuclear and cytoplasmic
compartments
- Electron microscopy reveals that the
envelope has two concentric membranes
separated by a narrow (30-50 nm)
perinuclear space
THE NUCLEUS  NUCLEAR LAMINA – a highly organized
meshwork of proteins that stabilizes the
nuclear envelope.
NUCLEUS
- a membrane-enclosed organelle that  NUCEAR PORE COMPLEXES – bridges
contains the cell’s DNA in chromosomes or the inner and outer nuclear membrane
chromatin, from which all types of RNA are
transcribed o Contain the machinery that regulates
- contains a blueprint for all cell structures most bidirectional transport between
and activities encoded in the DNA of the the nucleus and the cytoplasm
chromosomes
- main components are the nuclear envelope,  Regulate movement of
chromatin and nucleolus macromolecules between the
- usually appears as a large rounded or oval nucleus and cytoplasm
structure, often near the cell’s center, and is
typically the largest structure within the cell o Nucleoporins – core proteins of a
nuclear core complex that displays
8-fold symmetry across the lumen

A.2 CHROMATIN

- Composed mainly of coiled strands of DNA

bound to basic proteins called histones
- In humans each cell’s chromatin (except
that of eggs and sperm) is divided among
46 chromosomes (23 pairs)
- After DNA replication but before cell
division, each chromosome consists of two

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- identical chromatin units called chromatids
held together by complexes of cohesin
proteins.
 NUCLEOSOME – structural unit of DNA
and histones
2 CATEGORIES OF CHROMATIN
1. EUCHROMATIN - visible as finely
dispersed granular material in the electron
microscope and as lightly stained basophilic
areas in the light microscope
- Transcriptionally active
- Less condensed regions of chromosome
- Region where 30nm fiber forms radial loop
domains
2. HETEROCHROMATIN - appears as
coarse, electron-dense material in the
electron microscope and as intensely
basophilic clumps in the light microscope
- Transcriptionally inactive
- Tightly compacted regions of chromosome
- Radial loop domains compacted even
further
 CHROMOSOMES - formed when the
chromatin threads become tightly
condensed
- In humans, most tissues (somatic cells)
contain 22 pairs of autosomes and one pair
of sex chromosomes
A.3 NUCLEOLUS
- Generally spherical, highly basophilic
structure in the nuclei of cells active in
protein synthesis
- The intense basophilia of nucleoli is due not
to heterochromatin but to the presence of
densely concentrated ribosomal RNA
(rRNA) that is transcribed, processed, and
assembled into ribosomal subunits
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CELL CYCLE
CELL CYCLE
- The regular sequence of events that
produce new cells
4 DISTINCT PHASES OF CELL CYCLE
1. MITOSIS – period of cell division
 The only cell cycle phase that can
be routinely distinguished with the
light microscope
 FOUR MAJOR STAGES OF MITOSIS
 PROPHASE - The nucleolus
disappears and the replicated
chromatin condenses into
discrete threadlike
chromosomes, each consisting
of duplicate sister chromatids
joined at the centromere
- The two centrosomes with
their now-duplicated
centrioles separate and
migrate to opposite poles of
the cell and organize the
microtubules of the mitotic
spindle
- Late in prophase, lamins and
inner nuclear membrane are
phosphorylated, causing the
nuclear lamina and nuclear
pore complexes to
disassemble and disperse in
cytoplasmic membrane
vesicles
 METAPHASE - the
chromosomes have become
aligned at the equatorial plate as
a result of their attachments to
the dynamic microtubules of the
mitotic spindle organized by the
centrosomes. The spindle
consists of kinetochore
microtubules, polar microtubules
which interdigitate near the
equatorial plate, and shorter
astral microtubules anchoring the
spindle to the cell membrane
DELA CRUZ, MJA
TOLERO, KB
H-03 THE NUCLEUS

 ANAPHASE - sister chromatids 4. G2 – the gap between DNA duplication

(now called chromosomes and the next mitosis
themselves) separate and move  Proteins required for mitosis
toward opposite spindle poles by accumulate
a combination of microtubule
motor proteins and dynamic
changes in the lengths of the
microtubules as the spindle
poles move farther apart.
 TELOPHASE - The two sets of
chromosomes are at the spindle
poles and begin reverting to their
decondensed state
- The spindle depolymerizes
and the nuclear envelope
begins to reassemble around
each set of daughter
chromosomes
- A belt-like contractile ring of
actin filaments associated
with myosins develops in the
cortical cytoplasm at the
cell’s equator. During
cytokinesis at the end of
telophase, constriction of this
ring produces a cleavage
furrow and progresses until
the cytoplasm and its  Cell cycling is controlled by the sequential
organelles are divided into appearance of key cytoplasmic proteins, the
two daughter cells, each with cyclins, which bind cyclin-dependent
one nucleus kinases (CDKs).
 CDKs phosphorylate and activate the
2. G1 - the time gap between mitosis and enzymes and transcription factors whose
the beginning of DNA replication functions characterize each phase of the
 Longest and most variable part of cell cycle
the cycle  Progress through the cell cycle stages is
 A period of active RNA and protein monitored at checkpoints, including the G1
synthesis, including proteins restriction point; only when each phase’s
controlling progress through the cell activities are completed are the cyclins
cycle changed to trigger those of the next phase.
3. S PHASE - characterized by DNA
replication, histone synthesis, and the
beginning of centrosome duplication

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STEM CELLS AND TISSUE RENEWAL
STEM CELLS
- Occur in all tissues with rapid cell turnover;
they divide slowly in an asymmetric manner,
with one daughter cell remaining a stem cell
and one becoming committed toward
differentiation
- Cells committed to differentiate (transit
amplifying or progenitor cells) typically
divide more rapidly than stem cells before
slowing or stopping division to differentiate.
 Cells formed by progenitor cells may become
terminally differentiated, meaning that
renewed cycling cannot occur and the
specialized cells exist for only a short time.
 In tissues with stable cell populations, such as
most connective tissues, smooth muscle, and
the cells lining blood vessels, stem cells are not
readily apparent and differentiated cells appear
to undergo slow and episodic division to
maintain tissue integrity.
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MEIOSIS
MEIOSIS
- specialized process involving two unique
and closely associated cell divisions that
occurs only in the cells that will form sperm
and egg cells.
- special form of cell division in germ cells
(oocytes and spermatozoa) in which the
chromosome number is reduced from
diploid(2n) to haploid(n).
 It occurs in developing germ cells in
preparation for sexual reproduction.
Subsequent fertilization results in
diploid zygotes.
 DNA content of the original diploid
cell is doubled (4n) in the S phase
preparatory to meiosis.
A. This phase is followed by two
successive cell divisions that
give rise to four haploid cells.
B. In addition, recombination of
maternal and paternal genes
occurs by crossing over and
random assortment, yielding the
unique haploid genome of the
gamete.
SYNAPSIS
- An activity where the homologous
chromosomes of each pair (one from the
mother, one from the father) come together.
- During synapsis double-stranded breaks
and repairs occur in the DNA, some of
which result in reciprocal DNA exchanges
called crossovers between the aligned
homologous chromosomes.
STAGES OF MEIOSIS
1. Reductional Division (Meiosis I)
- occurs after interphase during the
cell cycle, when the DNA content is
duplicated, whereas the chromosome
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2. Equatorial Division (Meiosis II) begins
number (46) remains unchanged, giving the
soon after the completion of meiosis I, following a
cell a 4CDNA content (considered to be the total
brief interphase without DNA replication.
DNA content of the cell).
a. The sister chromatids are portioned out
a. Prophase I - is divided into five stages
among the two daughter cells formed in meiosis I.
(leptotene, zygotene, pachytene, diplotene, and
The two daughter cells then divide, resulting in the
diakinesis), which accomplish the following events:
distribution of chromosomes into four daughter
(1) Chromatin condenses into the visible cells, each containing its own unique recombined
chromosomes, each containing two chromatids genetic material (1CDNA;n).Thus, every gamete
joined at the centromere. contains its own unique set of genetic materials.

(2) Homologous maternal and paternal b. The stages of meiosis II are similar to
chromosomes pair via the synaptonemal complex, those of mitosis; thus, the stages are named
forming a tetrad. Crossing over (random similarly (prophase II, metaphase II, anaphase II,
exchanging of genes between segments of and telophase II).
homologous chromosomes) occurs at the
c. Meiosis II occurs more rapidly than
chiasmata, thus increasing genetic diversity.
mitosis.
(3) The nucleolus and nuclear envelope
disappear.
b. Metaphase I
(1)Homologous pairs of chromosomes align
on the equatorial plate of the spindle in a random
arrangement, facilitating genetic mixing.
(2) Spindle fibers from either pole attach to
the kinetochore of any one of the chromosome
pairs, thus ensuring genetic mixing.
c. Anaphase I
(1)This phase is similar to anaphase in
mitosis except that each chromosome consists of
two chromatids that remain held together.
(2) Chromosomes migrate to the poles.
d. Telophase I - is similar to telophase in
mitosis in that the nuclear envelope is reestablished
and two daughter cells are formed via cytokinesis.
(1) Each daughter cell now contains 23
chromosomes (n) number but has a 2CDNA
content (the diploid amount).
(2) Each chromosome is composed of two
similar sister chromatids (but not genetically
identical following recombination).

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APOPTOSIS

APOPTOSIS
- “Program cell death”
- A rapid, highly regulated cellular activity that
shrinks and eliminates defective and
unneeded cells.
- The method whereby cells are removed
from tissues in an orderly fashion as a part
of normal maintenance or during
development.

 Apoptosis is controlled by cytoplasmic

proteins in the Bcl-2 family, which
regulate the release of death-promoting
factors from mitochondria. Activated by
either external signals or irreversible
internal damage, specific Bcl-2 proteins
induce a process with the following
features:
o Loss of mitochondrial function
o Fragmentation of DNA
o Shrinkage of nuclear and cell
volumes
o Cell membrane changes
o Function and phagocytic removal of
these apoptotic bodies

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