Lecture 1: Developmental Biology

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Activity notes (hyperlink)

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Lecture 1: Developmental Biology



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Developmental BiologyEmbedded Assessment

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Draw a four-day old human embryo

1) Note the approximate size or scale2) Include as much detail as you can in 5 minutes



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The animal cell

Nucleus Plasma membrane

Mitochondrion

Golgi complex

Vacuole

Nuclear membrane

Endoplasmic reticulum

(ER)

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Multicellular organisms have a variety of

differentiated cell types

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Immature undifferentiated

cells

Stem cell

Progenitor cell

Mature differentiated cells(200 different cell types)

Neuron

Heart muscle cell(Cardiomyocyte)

Red and white blood cells

Epidermal skin 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

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The cell cycle Mitosis

Mitosis (M)

DNA synthesis (S)

Restingphase

(parental cell)Prophase

Anaphase

Telophase

Interphase (daughter cell)

Metaphase

Prometaphase



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Symmetric versus asymmetric cell division in

stem cells

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Symmetricstem cell division

Two stem cells

expansion

Stem cell

Progenitor

maintenance

Asymmetricstem cell division



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Meiosis

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First meiotic division(reduction division)

Second meiotic division(mitosis with DNA replication)

Prophase 1 (4n)

Metaphase 1

Anaphase 1

Telophase 1

Crossing over

Paternalhomolog

Maternal homolog

Prophase 2

Metaphase 2

Anaphase 2 Telophase 2

Two parental cells (2n)

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 organism’s genome

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Nucleus

DNAhelix

Duplicatedchromosome

Duplicatedchromosome gen

e



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The Central Dogma represents the flow of genetic information

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DNA RNA PROTEINTranscription Translation



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Transcription: DNA makes RNA

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Strand of DNA

Forming strand of mRNA

RNA polymerase

DNA RNATranscription



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Translation: RNA makes protein

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RNA PROTEINTranslation



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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

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Cell type

Unique protein

Motor neuron

Heart muscle cell

(Cardiomyocyte)

Red blood cells

Myosin Light Chain 2: causes

muscle contraction

Hemoglobin: transports oxygen

from lungs and carbon dioxide

from body

Choline Acetyltransferase: enzyme that produces the chemical signal for neuron-muscle communication



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Transcription factors regulate the flow of genetic information

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DNA RNA PROTEINSTranscription Translation

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 signaling molecules

• 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

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Gene expression

Motor neuron

Heart muscle cell

(Cardiomyocyte)

Red blood cells

ON

ON

ON OFF

OFF

OFF

OFF

OFF

OFF

-globin gene

ChAT gene

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

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Cell signaling pathways

Motor neuron

Heart muscle cell

(Cardiomyocyte)

Red blood cells

Progenitor cell

Progenitor

cell

Progenitor cell

Shh

Patched/ Smoothened

ErythropoietinEPO receptor

Activin/TGFBMPRI



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The beginning of human development

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)

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 male’s life.

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2N



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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.

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Meiosis I

Meiosis IIafter fertilization

Meiosis I

Primaryoocyte

Secondaryoocyte (2n)

Polar body (2n)

Egg (n) Polar bodies (n)

Embryo

Puberty



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Fertilization

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:

• 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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A sperm cell attempts to penetratethe ovum’s coat in order to fertilize it



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Cleavage (days 1-6)

1. Zygote divides into two cells

2. Day two: morula (Latin for mulberry)

3. Cell signaling begins

4. Embryo begins to organize

5. Blastocyst forms on days 4-6

6. Two parts of blastocyst

• Trophectoderm (placenta, amnion)

• Inner cell mass (embryo)

7. Size is 0.1 mm25

2 cell stage 4 cell stage

8 cell stage Morula

Blastocyst

Inner cell mass

Trophectoderm



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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 normallyderived from the inner cellmass of the blastocyst

3. ES cells can be derivedfrom primordial germ cells

4. ES cells can be derivedfrom adult somatic cells

[Figure modified from Gilbert’s “Developmental biology”, 8th edition, Sinauer]



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Embryogenesis (week 2): formation of germ layers

Blastocyst

Uterus

Ectoderm

Mesoderm

Yolk sac

Amnion

Endoderm

Epithelial skin cells, inner ear, eye,

mammary glands, nails, teeth,

nervous system (spine and brain)

Blood, muscle, bones, heart,

urinary system, spleen, fat

Stomach, gut, liver, pancreas, lungs,

tonsils, pharynx, thyroid glands

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Implantation



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Lineage restriction: differentiation into

specialized cells

differentiated cellsprogenitor cells

skin

heart

brain

Zygote ES cell

Ectodermal cell

Mesodermal cell

bonemarrow

PluripotentTotipotent Multipotent

Endodermal cell

gut



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The hematopoietic system as an example of lineage

restriction

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Multipotent stem cell

[Image taken from Gilbert’s “Developmental biology”, 8th edition, Sinauer].

Differentiated cell

Progenitor cell



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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

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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

Lecture 1: Developmental Biology

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