Lecture 1: Developmental Biology

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Lecture 1 Developmental Biology
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Developmental BiologyEmbedded Assessment

• Draw a four-day old human embryo
• Note the approximate size or scale
• Include as much detail as you can in 5 minutes

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The animal cell
Golgi complex
Endoplasmic reticulum (ER)
Mitochondrion
Nucleus
Plasma membrane
Nuclear membrane
Vacuole
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Multicellular organisms have a variety of
differentiated cell types
Immature undifferentiated cells
Mature differentiated cells (200 different cell
types)
Stem cell
Heart muscle cell (Cardiomyocyte)
Epidermal skin cells
Progenitor cell
Neuron
Red and white blood cells
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All cell types in a multicellular organism are
generated from a single cell
Image taken from Gilberts Developmental
Biology, 8th edition, Sinauer.
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The cell cycle and mitosis
The cell cycle
Mitosis
(parental cell) Prophase
Mitosis (M)
Prometaphase
Interphase (daughter cell)
Resting phase
Metaphase
Telophase
Anaphase
DNA synthesis (S)
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Symmetric versus asymmetric cell division in stem
cells
Symmetric stem cell division
Asymmetric stem cell division
expansion
maintenance
Progenitor
Stem cell
Two stem cells
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Meiosis
First meiotic division (reduction division)
Second meiotic division (mitosis with DNA
replication)
Paternal homolog
Two parental cells (2n)
Parental cell (2n)
Maternal homolog
Prophase 2
Prophase 1 (4n)
Crossing over
Metaphase 2
Metaphase 1
Anaphase 1
Anaphase 2
Telophase 2
Telophase 1
Four daughter cells (n)
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Chromosomes, genes and DNA

1. The nucleus contains genetic material in
   structures called chromosomes
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
4. Sequences of chemical bases make up genes
5. Animals share common genes
6. Genes are the basic units of heredity
7. Humans have 25,000 genes
8. The entirety of DNA in a cell is an organisms
   genome

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The Central Dogma represents the flow of genetic
information
Transcription
Translation
DNA
RNA
PROTEIN
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Transcription DNA makes RNA
Transcription
DNA
RNA
RNA polymerase
Strand of DNA
Forming strand of mRNA
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Translation RNA makes protein
Translation
RNA
PROTEIN
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Summary of gene expression

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

• 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
Heart muscle cell (Cardiomyocyte)
Motor neuron
Red blood cells
Unique protein
Hemoglobin transports oxygen from lungs and
carbon dioxide from body
Myosin Light Chain 2 causes muscle contraction
Choline Acetyltransferase enzyme that produces
the chemical signal for neuron-muscle
communication
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Transcription factors regulate the flow of
genetic information
Transcription
Translation
DNA
RNA
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

• Secreted proteins
• 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
Heart muscle cell (Cardiomyocyte)
Motor neuron
Red blood cells
Gene expression
ON
OFF
OFF
?-globin gene
OFF
ON
OFF
ChAT gene
ON
OFF
OFF
Myosin light chain 2 gene
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Differential gene expression underlies the
process of differentiation

• 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
Cell signaling pathways
Shh
Erythropoietin
Activin/TGF?
Patched/ Smoothened
BMPRI
EPO receptor
Progenitor cell
Progenitor cell
Progenitor cell
Heart muscle cell (Cardiomyocyte)
Motor neuron
Red blood cells
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The beginning of human development

• 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
• Fertilization
• One sperm one egg, chromosome number restored
• The genes from each are required for development
• Embryogenesis Formation of the embryo
• The zygote is the earliest form of a human embryo

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Spermatogenesis generation of male gametes
(sperm)

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 adult males
   life.

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Oogenesis generation of female gametes (oocytes)

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.
3. First meiotic division resumes at puberty.
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.

Meiosis I
Meiosis I
Embryo
Primary oocyte
Secondary oocyte (2n)
Polar body (2n)
Meiosis II after fertilization
Puberty
Egg (n)
Polar bodies (n)
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Fertilization

• Fusion of sperm and egg to create a new
  individual.
• The diploid cell is called a zygote.
• Restores the DNA content and combines genes from
  both parents (sexual reproduction).
• Major events in fertilization
• 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

A sperm cell attempts to penetrate the ovums
coat in order to fertilize it
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Cleavage (days 1-6)
2 cell stage
4 cell stage
8 cell stage
Morula

• Zygote divides into two cells
• Day two morula (Latin for mulberry)
• Cell signaling begins
• Embryo begins to organize
• Blastocyst forms on days 4-6
• Two parts of blastocyst
• Trophectoderm (placenta, amnion)
• Inner cell mass (embryo)
• Size is 0.1 mm

Blastocyst
Trophectoderm
Inner cell mass
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The origin of embryonic stem cells (ES cells)
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
Figure modified from Gilberts Developmental
biology, 8th edition, Sinauer
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Embryogenesis (week 2) formation of germ layers
Amnion
Implantation
Uterus
Blastocyst
Ectoderm
Yolk sac
Epithelial skin cells, inner ear, eye, 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
Pluripotent
Multipotent
Totipotent
brain
skin
Ectodermal cell
bone marrow
Zygote
ES cell
Mesodermal cell
heart
gut
Endodermal cell
differentiated cells
progenitor cells
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The hematopoietic system as an example of lineage
restriction
Multipotent stem cell
Progenitor cell
Differentiated cell
Image taken from Gilberts Developmental
biology, 8th edition, Sinauer.
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Summary

• 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
Create a concept map using the key concepts from
todays 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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