Gateway II Biosciences II: Growth and Development PDF

GATEWAY foundations in biosciences II L8. Growth and Development of Organisms Nobue Itasaki Learning objectives Appreciate the developmental stages in life from embryos to adulthood Understand basic embryogenesis Describe the role of hormones and growth factors in growth and development Appreciate t...

GATEWAY foundations in biosciences II L8. Growth and Development of Organisms Nobue Itasaki Learning objectives Appreciate the developmental stages in life from embryos to adulthood Understand basic embryogenesis Describe the role of hormones and growth factors in growth and development Appreciate the maintenance of adult bodies by stem cells Define the term senescence Human life cycle Embryonic development growth puberty maintenance ageing Embryogenesis Does embryo grow in a same speed every month? Learn the concept of critical period Development of Human Embryo 2 mm The overall structure is formed by the first two months The rest of the gestation period is mainly for the growth (3cm50cm) Human development overview (1) Day 1 2nd week 5th week 6th week 3rd week 7th week 4th week 8th week Human development overview (2) 9th week 10th week 11th week 13th week End of 1st trimester 28th week 2nd/3rd trimester 38 weeks http://www.babycenter.com/fetal-development-week-by-week Human embryonic development 0 4 8 12 16 20 24 28 32 weeks 36 38 (full term) “egg” (Germinal period) “embryo”(3rd - 8th weeks) “foetus” 4th week 7th week 1st trimester 2nd trimester 3rd trimester Two ways to count the age of embryos Embryonic age 0 4 8 12 16 20 weeks 24 28 32 36 38 birth fertilisation Clinical (“pregnancy”) stage 0 4 8 12 Day 1 of the last menstrual period (LMP) 16 20 24 28 weeks 32 36 40 “9 months + 7days” The Critical Period The developmental stage when an embryo is susceptible to toxic agents (teratogens) Usually corresponds to the stage of active differentiation and morphogenesis Varies depending on the organs (see next page) Possible teratogens: medications – e.g. thalidomide (sedative drug) alcohol, tobacco, caffeine environmental chemicals viral infection The critical period for organs Critical period (highly sensitive) Critical period (moderately sensitive) from Human Biology by Starr and McMillan Thalidomide Used as a sedative drug during 1959- 62 in Europe, Canada, Australia, Asia Popular due to low toxicity to adults Prescribed to pregnant women to treat nausea and vomiting caused by morning sickness Estimated 10,000 children were born with major malformations Critical period for thalidomide 0 4 8 12 16 20 24 “egg” “embryo”(3-8 weeks) “foetus” 4th week 7th week 28 32 weeks 36 38 (full term) The critical period for organs Critical period (highly sensitive) Critical period (moderately sensitive) from Human Biology by Starr and McMillan Implantation occurs at the blastocyst stage 2 cells (day 2) 1 cell (day 1) 4 cells (day 3) 8 cells (day 4) fertilised oocyte Implantation (day 8-9) Following gastrulation, three germ layers (ectoderm, mesoderm, endoderm) are formed ectoderm mesoderm endoderm Surface ectoderm Neural tube endoderm Derivatives of three germ layers Ectoderm surface ectoderm (mainly epidermis of the skin) the nervous system neural crest cell derivatives (melanocytes, some of skull bones, adrenal medulla) Mesoderm dermis (inner layer of the skin) muscles skeleton (bones and cartilages except in the head) urogenital organs (except urinary bladder) blood, vasculature, spleen Endoderm the digestive system (gut, liver, pancreas) the respiratory system urinary bladder thyroid, parathyroid Growth of foetus 1 2 3 4 1. Morphogenesis and Differentiation 2. Rapid growth 3. Protein accumulation 4. Fat accumulation Growth after birth Growth spurts at puberty – how? Hormones involved in growth Growth hormone (GH), Insulin-like Growth Factor-1 (IGF-1) Gonadotropin-releasing hormone (GnRH) Gonadal steroids (Androgens, Estrogens, Progesterone) Others (Thyroid hormones, calcitonin, parathyroid hormone, corticosteroids..) The lifetime pattern of GH secretion From: Human Physiology 4th Ed The effect of GH Stimulates glycogenolysis by the liver => raise plasma glucose level => make glucose available for glycolysis Repress glucose uptake by muscle and adipose tissue Stimulates lipolysis Stimulates amino acid uptake =>protein synthesis Cause production of IGF in the liver * GH/IGF-1 axis decrease in adults Associated with extended longevity in mice Pharmaceutical inhibition of GH might delay ageing and protect from cancer and diabetes mellitus Human Physiology 4th Ed Ch 36.4 Nature Reviews Endocrinology 9, 366-376 (2013) Gonadotropin HormoneReleasing Hormone (GnRH) Increasing activity of the hypothalamic GnRH-secreting neurons Increase of Follicle Stimulating Hormone (FSH) Luteinising hormone (LH) Up to age 10 puberty In females, ovarian follicles begin to mature In males, Leydig cells mature in response to LH => testosterone secretion, spermatogenesis Human Physiology 4th Ed Ch 33.4 Maintenance of adult body Our body structure is maintained partly by replacement of old cells by new cells Cell renewal Renew by stem cells Skin epidermis Intestinal epithelium Blood cells Olfactory neurons (e.g. in rodents) Renew without stem cells Insulin producing β-cells Hepatocytes in the liver (so far known as) Do not renew Auditory receptor cells Photoreception cells Stem cell ² Undifferentiated lack tissue-specificity or specialized functions ² Able to differentiate can give rise to specialized cell types via differentiation ² Self-renewal capable of renewing themselves by cell division for long periods i.e, undifferentiated state is maintained after cell division in at least one of daughter cells Stem cell divisions Stem cell categories Embryonic stem cell (ES cell) Adult stem cell Induced pluripotent stem (iPS) cell Fetal stem cell -- pluripotent --- multipotent --- pluripotent --- multipotent Adult stem cells Hematopoietic stem cells Dermal papilla cells, hair follicle stem cells Intestinal stem cells Other adult stem cells: Mesenchymal stem cells Limbal stem cells at the margin of cornea (limbus) => corneal epithelial stem cells Satellite cells in muscle Neural stem cells in subventricular zone, dentate gyrus of the hippocampus Example of adult stem cells: intestinal stem cells Intestinal stem cell ageing What is the difference between the cells of young individuals and elderly people? Quiescence (cell cycle arrest at G0 due to a lack of nutrition, no stimuli for cell division) Senescence (from G0 to cell death eventually, though the cells were metabolically active) Hallmark of ageing https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/ Ageing factors Accumulation of mutations and epigenetic changes in the genome At typical age of 70, a somatic cell has 2000 gene ‘scars’ (traces of DNA repair) across the genome Accumulation of mutations in mitochondrial DNA Mutation can occur x100 more frequently in mitochondria than in genome DNA due to toxic ROS (Reactive Oxygen Species) Mitochondria can fuse, as well as divide, thus exchange DNA and repair damaged one Senescence Most human cells divide only a limited number of times It is because the chromosome becomes shorter and shorter at their ends (telomere) Chromosome without telomere is detected as a DNA damage and the cell cycle is arrested by p53 => replicative cell senescence DNA damage response P53 Apoptosis Senescence AGEING P53 -/ Genomic instability CANCER Telomere Repetitive DNA sequences, (GGGTTA)n in human, at the end of chromosomes ~ 2,500 repeats in human At birth about ~ 2,000 => several hundreds in old age Forms a loop such that the end of the chromosome will not be recognised as broken DNA, protecting from damage and end-fusion DNA replication of this region requires telomerase (cannot be done by usual DNA replication method) -next slide Stem cells express high levels of telomerase hence able to replicate without a loss of the telomere region (the lost telomere could even be added by de novo synthesis) Most differentiated cells express only a low level of telomerase therefore loose 100200 nucleotides (15-30 repeats) every cell division Telomere shortening is a mechanism for cells to ‘count’ cell division: to get rid of old cells, also to self-guard against uncontrolled cell division DNA replication at the telomere With telomerase: 5’ 3’ 5’ 5’ Telomerase (a reverse transcriptase) with bound RNA template Without telomerase: 3’ 5’ 5’ DNA polymerase 5’ Telomere and ageing After birth Embryogenesis Telomere loss Telomere loss Telomere rejuvenation Intact p53 ageing Dysfunction of p53 cancer Telomere loss => DNA damage => p53 increases anti-proliferative DNA repair apoptosis Many cancer cells have regained the ability to express telomerase able to proliferate regardless of DNA damage iPS cells (induced pluripotent stem cells from somatic cells) also regain the ability to express telomerase Mouse without telomerase For your interest only Nature 464, 520–528 (2010) Mouse has x5 longer telomere than human to begin with Resembling dyskeratosis congenita in human (Heterozygous for non-functional telomerase) Prematurely shortened telomere Summary Embryogenesis morphogenesis at the first trimester Critical period Gastrulation => ectoderm, mesoderm and endoderm derivatives Birth and growth Different speeds of growth during life Hormonal regulation Maintenance of Adult body Stem cells Ageing Limited counts of cell division by telomerase References Human Physiology 4th Ed; Pocock Richards and Richards. Oxford Press Molecular Biology of the Cell, 6th Ed, chapter 5, 21; Alberts et al., Garland Science Nature Reviews Endocrinology 9, 366-376 (2013) GH/IGF and ageing Huang et al.,Telomere regulation in pluripotent stem cells https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967062/ Donate and Blasco Telomeres in cancer and ageing http://rstb.royalsocietypublishing.org/content/366/1561/76 Armstrong et al., Overexpression of telomerase confers growth advantage, stress resistance, and enhanced differentiation of ESCs toward the hematopoietic lineage https://www.ncbi.nlm.nih.gov/pubmed/15790773 Telomere end loop http://circresearch.com/gallery/tag/biomarkers/ Telomerase elongation in stem cells http://www.nature.com/nature/journal/v464/n7286/full/nature08792.html Low IGF1 => small body, but rarely develop cancer or age-related diseases https://www.bbc.co.uk/iplayer/episode/b01lxyzc/horizon-20122013-3-eat-fast-andlive-longer