Transcript Slide - Bio-Link

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Lecture 1: Developmental Biology
Developmental Biology
Embedded Assessment
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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
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The animal cell
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Golgi complex
Endoplasmic
reticulum (ER)
Mitochondrion
Nucleus
Plasma
membrane
Vacuole
Nuclear
membrane
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Multicellular organisms have a
variety of differentiated cell types
Immature
undifferentiated cells
Stem cell
Progenitor cell
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Mature differentiated cells
(200 different cell types)
Heart muscle cell
(Cardiomyocyte)
Neuron
Epidermal skin cells
Red and white
blood cells
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All cell types in a multicellular organism
are generated from a single cell
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[Image taken from Gilbert’s “Developmental Biology”, 8th edition, Sinauer].
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The cell cycle and mitosis
The cell cycle
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Mitosis
(parental cell)
Prophase
Mitosis (M)
Prometaphase
Interphase
Resting
phase
(daughter cell)
Metaphase
Telophase
Anaphase
DNA synthesis (S)
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Symmetric versus asymmetric cell
division in stem cells
Symmetric
stem cell division
expansion
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Asymmetric
stem cell division
maintenance
Progenitor
Two stem cells
Stem cell
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Meiosis
First meiotic division
(reduction division)
Paternal
homolog
Maternal
homolog
Crossing over
Parental
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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)
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Chromosomes, genes and DNA
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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
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The Central Dogma represents the
flow of genetic information
Transcription
DNA
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Translation
RNA
PROTEIN
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Transcription: DNA makes RNA
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Transcription
DNA
RNA
RNA polymerase
Strand of DNA
Forming strand of mRNA
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Translation: RNA makes protein
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Translation
RNA
PROTEIN
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Summary of gene expression
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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
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Proteins: the product of
translation
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• 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
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Various differentiated cell types
express different proteins
Cell type
Motor neuron
Heart muscle cell
(Cardiomyocyte)
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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
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Transcription factors regulate the
flow of genetic information
DNA
Transcription
RNA
Translation
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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.
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Signaling proteins are essential for
cell-cell communication
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• 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
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Differential gene expression underlies the
presence of distinct proteins in various cells
Motor neuron
Heart muscle cell
(Cardiomyocyte)
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Red blood cells
Gene expression
OFF
OFF
ON
-globin gene
ON
OFF
OFF
ON
OFF
ChAT gene
OFF
Myosin light chain 2 gene
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Differential gene expression underlies
the process of differentiation
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• 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.
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Differential cell signaling contributes to the
generation of cellular diversity
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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
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The beginning of human
development
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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
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Spermatogenesis: generation of
male gametes (sperm)
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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.
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Oogenesis: generation of female
gametes (oocytes)
Embryo
Meiosis I
Meiosis I
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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)
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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.
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Fertilization
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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
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Cleavage (days 1-6)
2 cell stage
4 cell
stage
8 cell stage
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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
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The origin of embryonic stem
cells (ES cells)
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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
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[Figure modified from Gilbert’s “Developmental biology”, 8th edition, Sinauer]
Embryogenesis (week 2):
formation of germ layers
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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
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Lineage restriction: differentiation
into specialized cells
Totipotent
Pluripotent
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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
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Multipotent stem cell
Progenitor cell
Differentiated cell
[Image taken from Gilbert’s “Developmental biology”, 8th edition, Sinauer].
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Summary
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• Immature (undifferentiated) cells
• Mature (differentiated) cells
• Differential gene expression
• Differential signaling pathways
• Fertilization
• Early embryogenesis
• Origin of ES cells
• Lineage restrictions
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Intro to Developmental Bio:
Concept Mapping Terms
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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
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