Processes of Cell Division

Processes of cell division, differentiation, and specialization Mitosis (BIO) • • • • • • Mitotic process: prophase, metaphase, anaphase, telophase, interphase o Prophase: condensation of chromatin into chromosomes, centrioles move to opposite poles of cell, microtubules begin to form o Metaphase: chromosomes align across equator of cell o Anaphase: sister chromatids pulled apart, cytokinesis begins o Telophase: nuclear membrane reforms, chromosomes de-condense, cytokinesis continues Mitotic structures o Centrioles, asters, spindles ▪ Centrioles: located in center of centrosomes, move to opposite ends of cell ▪ Asters: microtubules radiating from centrioles ▪ Spindle microtubules: microtubules connecting the two centrioles o Chromatids, centromeres, kinetochores ▪ Chromatid: two identical copies of a chromosome, joined together by a centromere ▪ Kinetochore: located at center of centromere of joined chromatids, structure of protein and DNA ▪ Kinetochore microtubules: connect centromeres to centrosomes/centrioles. • Their shortening pulls sister chromatids apart o Nuclear membrane breakdown and reorganization ▪ Starts to break down in anaphase, finishes in telophase ▪ Nuclear membrane reorganizes in telophase o Mechanisms of chromosome movement ▪ Kinetochore microtubule shortening pulls sister chromatids apart Phases of cell cycle: G0, G1, S, G2, M o G1: cell growth. Protein, RNA, and phospholipid synthesis highly active o G0: non-growing state, most protein production takes place here o S: preparing cell for mitosis, a lot of DNA replication o M: mitosis, division of nucleus o G2: cell prepares to divide, RNA and proteins (esp tubulin) are produced Growth arrest (cell arrested for many reasons) o Too much genomic mutation/damage causes cell to arrest in M phase o Contact inhibition: normal epithelial cells stop growing when it gets crowded such that it’s touching adjacent cells o Lack of food can also cause growth arrest Control of cell cycle o Checkpoints ▪ G1 checkpoint • If conditions are favorable for division → S; if not → G0 o Favorable conditions based on cell size (Large = ready) ▪ G2 checkpoint • Checks for mitosis promoting factor (MTF) o High MTF levels indicates aligned chromosomes → mitosis is triggered Loss of cell cycle controls in cancer cells o Two types of mutations that can cause cancer ▪ Deactivation of checkpoint protein (tumor repressor) ▪ Activation of gene causing proliferation of cell (oncogene) Biosignaling (BC) • Oncogenes, apoptosis • • • o Carcinogens can trigger transcription of oncogenes o Failure of normal cellular controls: ▪ Cancer cells continue to grow and divide in situations normal cells would not ▪ Cancer cells fail to respond to cellular controls/signals that would halt this growth ▪ Cancer cells avoid apoptosis (self-destruction) that normal cells undergo when extensive DNA damage is present ▪ Cancer cells stimulate angiogenesis (cause new blood vessels to grow to nourish the cancer cell) ▪ Cancer cells are immortal while normal cells die after a number of divisions ▪ Cells can metastasize – break off and then grow in another location Gated ion channels: let ions from one side of the membrane to another o Voltage gated: ▪ Na and K voltage gated ion channels: involved in action potential. Speed at which they open are different ▪ Ca2+ voltage gated channels: located at presynaptic side of synaptic cleft. Action potential causes channels to open, Ca2+ to flow into cell. This causes efflux of NT vesicles o Ligand gated Receptor enzymes: bind NT’s or hormones and triggers processes in cell o NT binding to receptor makes postsynaptic side more permeable to ions. This completes the transfer of the neural impulse o NT’s released back into cleft after binding to receptor ▪ Need ways to get rid of NT’s in cleft • Destroy using an enzyme in the cleft • Reabsorb into presynaptic cleft • Diffuse out of cleft G protein-coupled receptors o Example of secondary messenger system o Binding of NT to this receptor causes release of an attached G-protein’s alpha subunit o Alpha subunit release in postsynaptic neuron, has a variety of effects: ▪ 1) Activates separate specific ion channels ▪ 2) Activate a second messenger (ex: cAMP) ▪ 3) Activate intracellular enzymes ▪ 4) Activate transcription Reproductive System (BIO) • Gametogenesis by meiosis o Sperm production ▪ 1) Spermatogonia, diploid progenitor cells that give rise to sperm, undergo mitosis to produce two diploid copies called primary spermatocytes ▪ 2) Primary spermatocytes undergo meiosis I to produce two unique, haploid, secondary spermatocytes ▪ 3) Secondary spermatocytes undergo meiosis II to make spermatids ▪ 4) Spermatids undergo process of maturation where they lose cytoplasm, gain a tail to make mature sperm ▪ 5) Ejaculation sends them through vas deferens, into urethra, and then out of the penis ▪ Sperm production occurs in the seminiferous tubules ▪ Hormones influencing sperm production • FSH: stimulates Sertoli cells which surround and nurture spermatocytes and spermatids (FSH → Sertoli cells) • LSH: stimulates Leydig cells which release testosterone to stimulate germ cells to differentiate into sperm (LH → Leydig Cells) • • o Ovum production ▪ 1) Follicle (comprised of egg and zona pellucida, viscous substance around the egg) is formed in the ovaries ▪ 2) Theca cells grow around the follicle to form the secondary follicle ▪ 3) Theca cells secrete androgen when stimulated with LSH. Androgen is converted to estradiol and secreted into blood ▪ 4) Follicle grows and bulges from ovary ▪ 5) Estradiol levels rise rapidly, cause dramatic increase in LH secretion (luteal surge) ▪ 6) Luteal surge causes ovulation (bursting of follicle, release of egg) ▪ 7) Egg swept into Fallopian tube, remaining follicle left behind becomes the corpeus luteum, which secretes estradiol and progesterone throughout pregnancy or for two weeks before degrading into the corpus albicans if impregnation doesn’t occur ▪ Two divisions of ovarian cycle: • Follicular Phase: beings with development of follicle, ends at ovulation • Luteal Phase: begins at ovulation, ends with degeneration of corpus luteum into corpus albicans ▪ 3 Phases of the ovarian cycle: • 1) Menstruation (follicle first develops, ends as follicle matures) • 2) Proliferation Phase (follicle matures, ends at ovulation) • 3) Secretory Phase (ovulation and corpus luteum secretes progesterone, estradiol, ends as luteum degrades into albicans) Ovum and Sperm o Differences in formation ▪ Primary oocytes only made before birth in females. Occurs constantly after puberty in males ▪ Primary oocytes arrested in Prophase I until menstrual cycle releases hormone signal for meiosis to continue ▪ Secondary oocytes are not equal. One receives all the cytoplasm and becomes an actual secondary oocyte. Another doesn’t and becomes a polar body to be discarded ▪ Secondary oocyte arrested at metaphase II. Released from ovary and travels down fallopian tube • Meiosis only continues when oocyte is penetrated by sperm during fertilization o Differences in morphology ▪Sperm: separated into 3 sections (head, midpiece, and tail), very little cytoplasm • Head: contains genetic information, only parts that penetrate egg in fertilization • Midpiece: contains mitochondria which power tail • Tail: propels sperm through fallopian tube ▪ Ovum: non-motile = round o Relative contribution to next generation ▪ Sperm contributes DNA only (the egg actively destroys sperm mitochondria) ▪ Egg contributes DNA + everything else (mitochondria, organelles, epigenetics) Reproductive sequence: fertilization; implantation; development; birth o 1. Fertilization: sperm + egg → zygote o 2. Implantation: ▪ 1. Zygote ▪ 2. Morula (solid ball) ▪ 3. Blastula (sea urchins) or blastocyst (mammals) ▪ 4. The blastocyst is the one that implants in the endometrium o 3. Development: ▪ 1. Zygote ▪ 2. Blastocyst ▪ 3. Implantation ▪ 4. Gastrulation ▪ 5. Organogenesis o 4. Birth: ▪ Switch from getting oxygen from mom’s blood → breathing ▪ Switch from getting nutrients from mom’s blood → suckling ▪ Fetal circulation (which bypasses lungs and liver) → normal circulation (by closing off ducts and openings) o Note: One X chromosome is deleted in female somatic cells HOWEVER, both are present in female reproductive cells Embryogenesis (BIO) • Stages of early development (order and general features of each) o Fertilization ▪ 1) Enzymes in sperm acrosome (head) dissolve outer layer of egg (zone pellicuda) ▪ 2) Cell membranes of sperm head and oocyte fuse on contact, sperm nucleus enters cytoplasm of oocyte ▪ 3) Cortical reaction occurs, preventing other sperm from fertilizing same egg ▪ 4) Oocyte undergoes second meitotic division to become an ovum, releases second polar body ▪ 5) Nuclei of sperm and ovum fuse to make a zygote o Cleavage ▪ 1) Zygote multiplies to a morula o Blastula formation ▪ 1) Morula divides, makes blastocyst (hollow ball of cells with a small mass on one side) ▪ 2) Blastocyst lodges in uterus in a process called implantation, fuses with uterine tissue to form placenta ▪ 3) Placenta HCG prevents degeneration of corpus luteum ▪ 4) Intercell communication in blastula causes blastocyst cells to differentiate (inner cells become embryo, outer cells become placenta) o Gastrulation ▪ First cell movements ▪ Formation of primary germ layers (endoderm, mesoderm, ectoderm) o Neurulation ▪ Gastrulation develops into a neurula, notochord causes neural plate and neural tube to form via induction ▪ Cells close to neural tube become neural crest ▪ Ectoderm → brain and spinal cord (by folding into a tube) • Major structures arising out of primary germ layers o Endoderm – digestive tract, respiratory tracts, liver, pancreas, thymus, thyroid o Mesoderm – blood cells, connective tissues (bones, muscles, tendons) and various organs (kidneys, heart, gonads, dermis of skin) o Ectoderm – epidermis of skin, nervous system, eyes, spinal cord • Neural crest o Neural crest cells located at the tip of each neural fold ▪ Migrate outward to form the PERIPHERAL NERVOUS SYSTEM • Includes: o Sensory ganglia, autonomic ganglia, adrenal medulla, Schwann cells o Neural tube gives rise to the CENTRAL NERVOUS SYSTEM • Environment-gene interaction in development Mechanisms of Development (BIO) • Cell Specialization = commitment followed by differentiation o Determination = irreversible commitment to become a certain cell type o Differentiation = becoming a cell type and adopting its specialized functions ▪ Epidermal cells produce keratin to protect skin against abrasion ▪ Myocyte produce actin and myosin to make muscles contract ▪ Neurons make neurotransmitters to transmit electrochemical impulses o Tissue Types: ▪ Epithelial = skin, lining of organs ▪ Connective = blood, bone, tendons, ligaments, cartilage ▪ Nervous = brain, spinal cord, nerves ▪ Muscle = skeletal, smooth, and cardiac muscles • Cell-cell communication in development o Cells in blastula communicate with each other to coordinate development of placenta and embryo o Induction: one group of cells changing the behavior of an adjacent group of cells o Inducer: the one that sends the signal for the other to change o Responder: the one that gets the signal and changes ▪ For example, the optic vesicle is able to induce the ectoderm to develop into lens o Induction mechanisms: physical touching of cells (juxtracine) or by releasing chemicals (paracrine) • Cell Migration o Process by which neural crest cells travel to various locations in body (remember the PERIPHERAL NERVOUS SYSTEM, its everywhere!) • Pluripotency: Stem Cells o Stem cells in blastocyst are pluripotent (can become most cells, depends on location in blastula) • Gene regulation in development o Differential gene transcription: ▪ Modification of DNA (methylations) can shut off or turn on genes ▪ Modification of histones (methylations, acetylations) that wrap the DNA can shut off or turn on genes • Acetylation of histone proteins DECREASES positive charge on lysine residues and weakens interaction of DNA with histone o Results in open DNA = easier transcription • Methylation of genes often results in SILENCING of gene expression ▪ To make or not to make transcription factors can regulate what genes get transcribed o Differential RNA processing: ▪ Selecting what RNA make it outside the nucleus to be translated ▪ Alternative splicing of RNA o Translation regulation: ▪ Some mRNA is made to last longer than others (more proteins translated off of it), and some are made to be rapidly degraded (less proteins translated off of it) ▪ Selective inhibition of translation of stored RNA in the oocyte (get translated only when needed after fertilization) o Post-translational regulation ▪ Some proteins are inactive until modified by certain enzymes ▪ Active proteins can be selectively marked for degradation by ubiquitin • Programmed cell death o Regulated by protein activity (not at level of transcription or translation) • Existence of regenerative capacity in various species • o Some systems (skin, liver, and blood) have multipotent stem cells which can regenerate these systems as needed (since these systems are injured or lost often) Senescence and aging o Senescence: process by which cells stop proliferating in response to environmental stressors and are cleared away by immune cells (allows for shaping of tissues) → Loss of cell’s power of division and growth (as you age ya know) ▪ Implicated in aging