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References Lecture notes (hyperlink) Activity notes (hyperlink) More links… Lecture 1: Developmental Biology Developmental Biology Embedded Assessment References Lecture notes (hyperlink) Activity notes (hyperlink) More links… Draw a four-day old human embryo 1) Note the approximate size or scale 2) Include as much detail as you can in 5 minutes 1 References The animal cell Lecture notes (hyperlink) Activity notes (hyperlink) More links… Golgi complex Endoplasmic reticulum (ER) Mitochondrion Nucleus Plasma membrane Vacuole Nuclear membrane 2 Multicellular organisms have a variety of differentiated cell types Immature undifferentiated cells Stem cell Progenitor cell References Lecture notes (hyperlink) Activity notes (hyperlink) More links… Mature differentiated cells (200 different cell types) Heart muscle cell (Cardiomyocyte) Neuron Epidermal skin cells Red and white blood cells 3 All cell types in a multicellular organism are generated from a single cell References Lecture notes (hyperlink) Activity notes (hyperlink) More links… [Image taken from Gilbert’s “Developmental Biology”, 8th edition, Sinauer]. 4 References The cell cycle and mitosis The cell cycle Lecture notes (hyperlink) Activity notes (hyperlink) More links… Mitosis (parental cell) Prophase Mitosis (M) Prometaphase Interphase Resting phase (daughter cell) Metaphase Telophase Anaphase DNA synthesis (S) 5 Symmetric versus asymmetric cell division in stem cells Symmetric stem cell division expansion References Lecture notes (hyperlink) Activity notes (hyperlink) More links… Asymmetric stem cell division maintenance Progenitor Two stem cells Stem cell 6 References Meiosis First meiotic division (reduction division) Paternal homolog Maternal homolog Crossing over Parental Lecture notes (hyperlink) Activity notes (hyperlink) More links… Second meiotic division (mitosis with DNA replication) (2n) Prophase 1 (4n) Metaphase 1 Two parental cells (2n) Prophase 2 Metaphase 2 Anaphase 1 Telophase 1 Anaphase 2 Telophase 2 Four daughter cells (n) 7 Chromosomes, genes and DNA References Lecture notes (hyperlink) Activity notes (hyperlink) More links… 1. The nucleus contains genetic material in structures called chromosomes Nucleus Duplicated chromosome 2. Chromosomes are long strands of DNA wrapped around a protein core 3. DNA is made of four chemical bases: A, T, C and G Duplicated chromosome 4. Sequences of chemical bases make up genes 5. Animals share common genes DNA helix 6. Genes are the basic units of heredity gene 7. Humans have ~25,000 genes 8. The entirety of DNA in a cell is an organism’s genome 8 The Central Dogma represents the flow of genetic information Transcription DNA References Lecture notes (hyperlink) Activity notes (hyperlink) More links… Translation RNA PROTEIN 9 Transcription: DNA makes RNA References Lecture notes (hyperlink) Activity notes (hyperlink) More links… Transcription DNA RNA RNA polymerase Strand of DNA Forming strand of mRNA 10 Translation: RNA makes protein References Lecture notes (hyperlink) Activity notes (hyperlink) More links… Translation RNA PROTEIN 11 Summary of gene expression References Lecture notes (hyperlink) Activity notes (hyperlink) More links… 1. Begins with genes in the nucleus 2. Genes have a code consisting of A, T, C and G 3. The code is “transcribed” into RNA (a messenger) 4. Messenger RNA (mRNA) brings the code to the cytoplasm 5. The genetic code uses groups of three bases (CCG, GUU) to encode each amino acid of a protein chain 6. Groups of three bases specify unique amino acids 7. Amino acids are the building blocks of proteins 8. Proteins are long chains of amino acids 12 Proteins: the product of translation References Lecture notes (hyperlink) Activity notes (hyperlink) More links… • Hemoglobin (carries oxygen in blood) • Insulin (regulates sugar breakdown/storage) • Enzymes (catalyze biochemical reactions) • Skin and hair color pigments • Signaling molecules – Control cell division – Coordinate development – Help ward off infection 13 Various differentiated cell types express different proteins Cell type Motor neuron Heart muscle cell (Cardiomyocyte) References Lecture notes (hyperlink) Activity notes (hyperlink) More links… Red blood cells Unique protein Choline Acetyltransferase: enzyme that produces the chemical signal for neuronmuscle communication Myosin Light Chain 2: causes muscle contraction Hemoglobin: transports oxygen from lungs and carbon dioxide from body 14 Transcription factors regulate the flow of genetic information DNA Transcription RNA Translation References Lecture notes (hyperlink) Activity notes (hyperlink) More links… PROTEINS Gene regulation • Some proteins termed “transcription factors” regulate the flow of genetic information. • These are nuclear proteins capable of binding DNA. • They regulate the process of gene transcription in immature and differentiated cells. • Transcription factors are essential for the processes of development and stem cell maintenance. 15 Signaling proteins are essential for cell-cell communication References Lecture notes (hyperlink) Activity notes (hyperlink) More links… • Secreted proteins Secreted signaling molecules • Form gradients when secreted from cells • Function by binding proteins at the surface of plasma membrane known as receptors • Activate intracellular proteins that relay information from the surface to inside the cell 16 Differential gene expression underlies the presence of distinct proteins in various cells Motor neuron Heart muscle cell (Cardiomyocyte) References Lecture notes (hyperlink) Activity notes (hyperlink) More links… Red blood cells Gene expression OFF OFF ON -globin gene ON OFF OFF ON OFF ChAT gene OFF Myosin light chain 2 gene 17 Differential gene expression underlies the process of differentiation References Lecture notes (hyperlink) Activity notes (hyperlink) More links… • Every nucleus contains a complete genome established in the fertilized egg (with a few exceptions). • The mouse genome contains tens of thousands of genes but many are not expressed in all tissues. • Many genes are differentially expressed in various tissues or organs. • Unused genes in differentiated cells are not destroyed or mutated - they retain the potential to be expressed. • Only a small percentage of the genome is expressed in each cell. 18 Differential cell signaling contributes to the generation of cellular diversity References Lecture notes (hyperlink) Activity notes (hyperlink) More links… Cell signaling pathways Shh Patched/ Smoothened Progenitor cell Motor neuron Activin/TGF Erythropoietin BMPRI EPO receptor Progenitor cell Heart muscle cell (Cardiomyocyte) Progenitor cell Red blood cells 19 The beginning of human development References Lecture notes (hyperlink) Activity notes (hyperlink) More links… 1. Gametogenesis: formation of eggs and sperm • Oocytes and spermatocytes (23 chromosomes) • Chromosomes in gametes are reduced by half • The story of sperm • The story of eggs 2. Fertilization • One sperm + one egg, chromosome number restored • The genes from each are required for development 3. Embryogenesis: Formation of the embryo 4. The zygote is the earliest form of a human embryo 20 Spermatogenesis: generation of male gametes (sperm) References Lecture notes (hyperlink) Activity notes (hyperlink) More links… 1. Meiosis produces four sperm cells from one germ cell (spermatogonium). 2. First division is a reduction division (separates homologous chromosomes that have been duplicated prior to meiosis; DNA content reduced from 4n to 2n). 3. Second division is a mitosis without DNA replication, generating haploid cells (n chromosomes). 4. Spermatogenesis occurs throughout an 2N adult male’s life. 21 Oogenesis: generation of female gametes (oocytes) Embryo Meiosis I Meiosis I Lecture notes (hyperlink) Activity notes (hyperlink) More links… 1. Oogenesis: meiosis that produces one egg and three polar bodies. 2. First meiotic division begins in the female embryo but stops before homologous chromosomes are separated. Primary oocyte Secondary oocyte (2n) 3. First meiotic division resumes at puberty. Polar body (2n) Meiosis II after fertilization Puberty Egg (n) References Polar bodies (n) 4. The second meiotic division occurs after fertilization, before sperm and egg nuclei fuse. 5. Females lose many germ cells over the course of their lifetime. 22 Fertilization References Lecture notes (hyperlink) Activity notes (hyperlink) More links… 1. Fusion of sperm and egg to create a new individual. 2. The diploid cell is called a zygote. 3. Restores the DNA content and combines genes from both parents (sexual reproduction). 4. Major events in fertilization: • • • A sperm cell attempts to penetrate the ovum’s coat in order to fertilize it • • Sperm and egg recognize and contact each other Block of polyspermy Second meiotic division of secondary oocyte (2n) to produce egg (n) Fusion of female and male pronuclei Stimulation of zygotic metabolism and cell cleavage 23 References Cleavage (days 1-6) 2 cell stage 4 cell stage 8 cell stage Lecture notes (hyperlink) Activity notes (hyperlink) More links… Morula 1. Zygote divides into two cells 2. Day two: morula (Latin for mulberry) 3. Cell signaling begins Blastocyst Trophectoderm 4. Embryo begins to organize 5. Blastocyst forms on days 4-6 Inner cell mass 6. Two parts of blastocyst • Trophectoderm (placenta, amnion) • Inner cell mass (embryo) 7. Size is 0.1 mm 24 The origin of embryonic stem cells (ES cells) References Lecture notes (hyperlink) Activity notes (hyperlink) More links… 1. ES cells can be derived from the morula 2. ES cells are normally derived from the inner cell mass of the blastocyst 3. ES cells can be derived from primordial germ cells 4. ES cells can be derived from adult somatic cells 25 [Figure modified from Gilbert’s “Developmental biology”, 8th edition, Sinauer] Embryogenesis (week 2): formation of germ layers References Lecture notes (hyperlink) Activity notes (hyperlink) More links… Amnion Implantation Uterus Blastocyst Ectoderm Epithelial skin cells, inner ear, eye, Yolk sac mammary glands, nails, teeth, nervous system (spine and brain) Endoderm Stomach, gut, liver, pancreas, lungs, tonsils, pharynx, thyroid glands Mesoderm Blood, muscle, bones, heart, urinary system, spleen, fat 26 Lineage restriction: differentiation into specialized cells Totipotent Pluripotent References Lecture notes (hyperlink) Activity notes (hyperlink) More links… Multipotent brain skin Ectodermal cell Zygote bone marrow ES cell Mesodermal cell heart gut Endodermal cell progenitor cells differentiated cells The hematopoietic system as an example of lineage restriction References Lecture notes (hyperlink) Activity notes (hyperlink) More links… Multipotent stem cell Progenitor cell Differentiated cell [Image taken from Gilbert’s “Developmental biology”, 8th edition, Sinauer]. 28 Summary References Lecture notes (hyperlink) Activity notes (hyperlink) More links… • Immature (undifferentiated) cells • Mature (differentiated) cells • Differential gene expression • Differential signaling pathways • Fertilization • Early embryogenesis • Origin of ES cells • Lineage restrictions 29 Intro to Developmental Bio: Concept Mapping Terms References Lecture notes (hyperlink) Activity notes (hyperlink) More links… Create a concept map using the key concepts from today’s lecture. You should include (but are not limited to) the following terms/concepts. Due by ___date_____: • Stem cells • Transcription • Translation • Chromosome • Gene • Cell signaling • Signal transduction • Differentiation • Germ layers • Ectoderm • Mesoderm • Endoderm • Blastocyst 30