Cell Cycle and Cyclins

Cell Cycle

• G0 phase: Cells stop dividing
• G1 phase: Cells double in size, organelle count, and other molecules
• Interphase: Includes G1, S, and G2 phases
• S phase: DNA and associated proteins are duplicated
• G2 phase: Cells prepare for division, with chromosomes beginning to condense
• Division: Includes mitosis, which separates two sets of chromosomes
• Cell cycle begins with the initiation of a new round of division

Cyclins

• Regulatory proteins control cyclin-dependent kinases (CDKs).
• CDKs phosphorylate proteins, triggering cell cycle processes
• G1 cyclins: Bind to kinases in G1, which are necessary to pass the G1 checkpoint and enter S phase
• Mitotic cyclins: Bind in G2 and are required to pass the G2 checkpoint and begin mitosis

Cell Cycle Checkpoints

• G1 checkpoint: Evaluates DNA integrity, nutrient availability, and cell size to initiate S phase
• G2 checkpoint: Verifies DNA duplication and cell size to initiate M phase
• Metaphase/spindle checkpoint: Confirms chromosome alignment before anaphase

DNA Replication in S Phase

• Enzymes unwind and "open" DNA by breaking hydrogen bonds between strands (5' to 3' direction)
• Each strand serves as a template, creating complimentary new strands such that A pairs with T, and C pairs with G

Mitosis and Meiosis

• Interphase involves DNA duplication before cell division
• Prophase: Chromosomes become visible and the spindle forms
• Metaphase: Chromosomes align at the cell's equator, attaching to microtubules
• Anaphase: Sister chromatids separate and move to opposite poles
• Telophase: Two nuclei form
• Cytokinesis:
  • Mitosis results in two diploid daughter cells from one parent cell
  • Meiosis I results in two haploid cells
  • Meiosis II results in four haploid cells

Meiosis-Specific Events

• Meiosis I includes homologous chromosome pairing and crossing over
• Homologous pairs align on the equator in metaphase I and separate in anaphase I
• In metaphase II, chromosomes align on the equator
• Anaphase II involves the separation of sister chromatids.

Heredity

Mendel’s First Law

• Alleles are variants of genes
• Phenotype: Observable characteristics resulting from genotype
• Genotype: The set of genes inherited by an organism from its parents
  • Homozygous dominant (AA): 0
  • Heterozygous (Aa): 4
  • Homozygous recessive (aa): 0
  • Phenotype ratio of 4:0
• Dominant allele (represented by A) and recessive allele (represented by a)

Mendel's Second Law

• Genotype
  • (AA): 1
  • (Aa): 2
  • (aa): 1
• Phenotype ratio of 3:1 (3 Yellow, 1 Green)

Mendel's Third Law

• Inheritance patterns with multiple traits are covered such as Yellow/round vs. Green/wrinkled with a ratio of 9:3:3:1

Inheritance Linked to the X Chromosome

• In Women:
  • Affected: XdXd
  • Healthy Carrier: XDXd
  • Healthy: XDXD
• In Men:
  • Affected: XdY
  • Healthy: XDY
• Example: Cross between a carrier female and a healthy male will result in a healthy daughter, a carrier daughter, a healthy son and an affected son

Gametogenesis

Oogenesis

• Oogonium develops into a primary oocyte, which is arrested in prophase I
• Primary oocyte produces a secondary oocyte and a polar body via meiosis I
• Secondary oocyte undergoes meiosis II to produce an ovum and another polar body

Spermatogenesis

• Spermatogonia develop into primary spermatocytes (2n)
• Primary spermatocytes undergo meiosis I, resulting in secondary spermatocytes (n)
• Secondary spermatocytes undergo meiosis II, developing into spermatids
• Spermatids undergo differentiation to become spermatozoa

Fertilization

• Penetration of corona radiata
• Acrosomal reaction with sperm releasing enzymes to penetrate zona pellucida
• Fusion of membranes
• Block to polyspermy
• Fusion of pronuclei to form a zygote.

Embryology

Ovary

• Secretes hormones (estrogen and progesterone) into the bloodstream internally
• Produces oocytes externally

Testicle

• Secretes testosterone into the bloodstream internally, and sperm are produced externally

Female Sexual Cycle

• Typically lasts 28 days and comprises three phases
• Menstrual Phase (Days 1-5): Hormone levels are low, and the endometrium is thin
• Proliferative Phase (Days 5-14): Estrogen is high and progesterone is low; the endometrium thickens
  • LH and FSH peak due to pituitary gland

Secretory Phase (Days 14-28)

• Progesterone is high which results in a thick endometrium, development of the corpus luteum
• After fertilization, the released oocyte travels through the fallopian tubes, dividing and developing into a morula around day 4, eventually reaching the uterus and becoming a blastula
• On day 6, implantation begins with the blastocyst attaching around 16–32 cells
• Implantation happens in the posterior wall of the upper third of the uterus and has three stages
  • Apposition: The embryo contacts the endometrial epithelium
  • Adhesion: membranes of the embryo and epithelium adhere
  • Invasion: The embryo passes through the epithelium

Second Week of Development

• The embryo develops into a bilaminar structure with two layers
  • Epiblast: gives rise to amniotic cavity
  • Hypoblast: forms yolk sac
• Trophoblast differentiates into cytotrophoblast and syncytiotrophoblast, and lacunae appear in the trophoblastic

Days 11/12

• Maternal sinusoids connect with trophoblastic lacunae, which fill with blood Two layers form:
  • Splanchnopleura
  • Somatopleura
• Day 13: Microvilli form, starting with primary, then secondary (day 16), and tertiary

Placenta

• Decidua (maternal component)
• Chorion Frondosum (embryonic component)
• Maternal Circulation:
  • Spiral arteries supply oxygen
  • Uterine veins remove CO2

Third Week of Development

• Gastrulation: Epiblast cells migrate to form the primitive streak;
  • Endoderm: Formed when some cells from epiblast migrate there to the hypoblast, gives rise to digestive and respiratory systems, liver, pancreas, and bladder
  • Mesoderm: Is Located amid the epiblast and hypoblast layers:
    • Paraxial: forms Somites
    • Intermediate: forms the urogenital system
    • Lateral: forms the cardiovascular system and serous membranes
  • Ectoderm: Formed by remaining cells in epiblast, which Gives rise to the skin, nervous system, eyes, and dental enamel

Notochord

• Originates from the primitive node, acts as the central axis of the embryo, guides vertebral column formation and induces neural tube formation to originate neural plate and the CNS
• Somites from the paraxial mesoderm divide into three portions
  • Sclerotome: Vertebrae and ribs
  • Myotome: Muscle
  • Dermatome: Skin and connective tissue

Fourth Week of Development

• Embryo undergoes folding:
  • Dorsoventral: Transforms the flat embryo into a cylinder
  • Cranio-caudal: Ends move toward the center With heart and vessel development beginning on day 22
• Limb buds (arms and legs) are visible
• Pharyngeal arches develop, which form the face, neck, and respiratory system. Nerves, blood vessels, and cartilage grow together

Derivatives of the Primitive Digestive Tube

• Foregut: Esophagus, duodenum, liver, pancreas, and respiratory system
• Hindgut: Descending colon to part of the anal canal and bladder
• Midgut: The distal half of the duodenum, jejunum, ileum, cecum, appendix, ascending colon, and proximal 2/3 of transverse colon

Derivatives of the Plates

• Roof plate: Forms the dorsal part of the ventricles
• Floor plate: Plays a minor role, mainly involutes
• Alar plate: Forms interneurons
• Basal plate: Forms neurons which innervate muscles to form motor section/motoneurons

Pronephros

• The mesoderm is used to develop the urinary system and a portion of the reproductive system. in there steps
• Is located in the cervical area (Som. 4) but is nonfunctional and degenerates
• Mesonephros (Som 4-8) This is located in the thoraco-lumbar, area functions Temporarily
  • In men, it forms the epididymis, ductus deferens, and seminal vesicles
  • In women, this degenerates

Metanephros

• Located in the lumbar region (sems - definitive kidney), it Forms from the ureteric bud and the metanephric blastema and initiates in weeks 9–10

Heart Development

Heart Looping and degeneration of the Dorsal Mesocardium

• A cardiogenic field is present, where the heart will develop, two cardiac tubes emerge which fuse to produce the primitive cardiac tube
• This expands and divides into four primary areas that will grow the heart
• Plication and rotation of the cardiac tube which enables the auricle to travel higher and assume its designated posture

Atrial Septation

• The septum primum is created which appears like a membrane that extends from the roof of the primitive auricle to the endocardial cushion and creates ostium primum which enables blood flow and to prevent blood clots
• The ostium secundum is developed when the ostium primum closes while allowing this to sustain fetal vascularity
• A foramen ovale is left on the right of the septum primum as the Septum secundum partially develops, upon delivery with the first breaths that increase blood flow to the left atrium, forcing the septum primum against the septum secundum and shutting off the foramen ovale

Primitive Circulatory System

• Organized into three systems
  • Vitelino: Collects blood from the vitelline sac and digestive tube, forming the portal vein, connecting to the liver where veins flow to the inferior vena cava
  • Umbilical: The umbilical vein transports oxygenated blood from the placenta to the heart
  • Cardinal: shapes the superior and inferior vena cava (earlier named anterior and posterior)
• The cardiac veins are reduced in evolution alongside the umbilical and vitelline veins
  • The coronary sinus accumulates coronary venous and draws the blood from the heart into the right atrium
  • The vitelline and umbilical veins disappear in the right venal sinus, in the liver veins attach to the inferior and superior vena cava

Fetal Blood Flow

• Oxygen rich blood enters the right atria from the umbilical cord
• Some blood then passes through the atrioventricular valve to the left atria
• Other blood goes to right ventricule and there to pulmonary arteries whichconnects through the arterial ductus