Chapter 21- Development and Gene Expression

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Chapter 21- Development and Gene Expression

• Central questions
• How are cells in various locations of the body
  different -is the variation in their genome or in
  the proteins they express?
• Can differentiated cells be coaxed to retrace
  their steps and become de-differentiated?
• How do cells become different from one another
  to form different body parts when they all
  develop from ONE cell - the zygote?
• Are there difference or similarities in the way
  genes behave during development between various
  species?

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Figure 21.1 From early embryo to tadpole what a
difference a week makes
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Types of stem cells Embryonic totipotent Embryoni
c pluripotent Adult stem cell (misnomer)
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Embryonic development single-celled zygotes 2
cell stage 4 cell stage Blastula (hollow ball
with cells on the outside). Humans - this is
called blastocyst
A cell from the blastula/blastocyst is also an
embryonic stem cell - it is able to differentiate
into many types of cells but not a full organism
- pluripotent!
A cell upto the 8 cell stage is an embryonic
stem cell - it is able to differentiate into a
full organism - totipotent!
Embryonic blastocyst stem cells in animals are
pluripotent because epigenetic modifications are
minimal- that is DNA methylation/histone
acetylation (turning off its genes) is minimal
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Embryonic development Blastula Gastrula (Ectoder
m, Mesoderm, Endoderm) Tissues Organs Organ
Systems
Once the cell is committed to its fate during
gastrula formation, they become differentiated -
they lose their pluripotency (genes turned off)!
Adults/babies (humans ) have adult stem cells -
in special places like the bone marrow which are
also pluripotent but to a lesser degree than
embryonic stem cells!
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Stem Cells In The Human Adult

• Bone Marrow Cells make blood cells all through
  life
• Brain Stem Cells can make neurons and glial
  cells
• Skin stem cells keratinocytes, hair follicles,
  epidermis
• Are human stem cells PLURIPOTENT? (-can
  differentiate into multiple cell types)
• Yes, but to a limited extent

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Stem Cells - another property

• Stem Cells have telomerase (immortal) - capable
  of self-renewal

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Cell division (mitosis) of the zygote increases
the number of cells in an organism. Differentiati
on is when each cell becomes specialized in both
structure and function (genes turned off by
epigenetic processes). Morphogenesis is when the
eventual shape (body plan) of the organism forms
- head-tail axes top-down axes.
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Plants Animals
N/A Movement of cells and tissue needed to transform embryo
Continuous differentiation, and morphogenesis throughout life Differentiation only during embryonic development and in some adult stem cells like bone marrow cells
Any cell in a plant can be a stem cell at any stage - totipotent. Meristems - regions of growth and differentiation. Totipotent - only upto 8 cell embryonic cell stage Pluripotent - blastocyst, bone marrow adult stem cells (can only make certain type of cells like blood cells)
If pluripotent - this means some genes are still
off (epigenetics)!
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Carrot cells are totipotent.

• In plants, cells remain totipotent
• all genes can be activated, and any cell
• can form any part of the organism

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Review Questions

• Are there differences in gene number or type
  between undifferentiated (stem) cells and
  differentiated (mature/adult) cells?
• Are there stem cells in an adult human body?
  Where?
• Can adult differentiated cells be induced to make
  any (and all) types of body cells - retrace and
  become embryo like?

NO! And Yes! And Yes!
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• Are there differences in genes between different
  cells in the body?
• No Genomic Equivalence
• Are there differences in genes expression between
  undifferentiated (stem) cells and differentiated
  (mature/adult) cells?
• Yes. Genes get inactivated/activated through
  processes like methylation (epigenetics)
• When cells differentiate, are genes
• inactivated irreversibly? Can they retrace to
  become de-differentiated?
• Well, it depends on the organism! Dec 2007 -
  scientists de-differentiated the human skin cells
  by using transcription factors!

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Can adult skin cells retrace steps to become
de-differentiated?

• Somatic Cell Nuclear transfer (SCNT)
• Take egg cell and remove nucleus (haploid) -
  throw it away
• Take skin cell and remove nucleus (diploid) -
  save this
• Insert skin cell nucleus (somatic cell) into egg
  cell cytoplasm. No need for sperm! Why?
• Allow egg cell to divide and become blastocyst
• Now you can extract stem cells (THERAPEUTIC
  CLONING) OR carry out REPRODUCTIVE CLONING -
  implant blastocyst in a surrogate mom and grow a
  clone!

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Dolly and Bonny!

• Reproductive Cloning is an offshoot of stem cell
  research

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SCNT made Dolly the sheep! -Mammary gland cells
from donor arrested in G0 phase
apparently dedifferentiated.
Review Dollys mitochondrial DNA is from the egg
donor sheep.
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Remember in cloning - an egg nucleus is replaced
with a nucleus of a differentiated cell. Ability
of differentiated nucleus to support normal
development is related to its age - Dolly may
have died prematurely and developed arthritis at
a young age! (epigenetics controls this)
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• Therefore in animals - review
• Nuclei change as cells differentiate
• The DNA sequence usually doesnt change, but
  chromatin structure may be altered
• Nuclear potency is restricted as cells
• develop and become more differentiated.

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Ques. 3) How do cells become different from one
another to form different body parts when they
all develop from ONE cell - the zygote?
How does a stem cell make a differentiated
cell? Determination differentiation of muscle
cells
What turns on the Master control gene?
Master control gene gt codes for transcription
factors gt turned on (determination) gt
transcription factors gt turs on other genesgt
more transcription factors gt muscle protein
genes turned on gt muscle protein (myosin) made
gt cell has differentiated (These are INTERNAL
SIGNALS)
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Figure 21.9 Determination and differentiation of
muscle cells (Layer 1)
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Figure 21.9 Determination and differentiation of
muscle cells (Layer 2)
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Figure 21.9 Determination and differentiation of
muscle cells (Layer 3)
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• Model organisms for development studies
• observable embryos
• short generation times
• relatively small genomes
• knowledge about the organism and its genes
• Drosophila, C. elegans, mouse, zebrafish,
• Arabidopsis

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• What tells a cell (and triggers the master gene)
  what its fate will be?
• Cytoplasmic determinants (from the mom -
  internal signals in egg)
• Inductionsignal molecules from cells
• nearby (neighbors)

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1) Cytoplasmic determinants include mRNA,
proteins, chemicals, and organelles and how they
are distributed in the egg. They are distributed
unevenly - and this can set up gradients that
says head side, tail side , etc.
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Cytoplasmic determinants are coded for by
maternal effect genes (or egg-polarity genes)
Example --Bicoid mRNA is present at the anterior
end of the egg -Bicoid protein is essential for
head formation.
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Background on Drosophila Cytokinesis does not
occur in the early Drosophila embryo. Nuclei
migrate to the periphery in the blastula.
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Bicoid is a morphogena substance that
establishes an organisms axis or other
3D features. Bicoid helps create the
anterior/posterior axis. Its a transcription
factor that activates expression of segmentation
genes
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• 3 types of segmentation genes
• Gap genes map out basic subdivisions along
• anterior/posterior axis
• Pair-rule genes define smaller regions
• Segment-polarity genes determine the
• anterior/posterior axis of each specific
• segment.

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• 2) Induction signals impinging on an embryonic
  cell from other nearby embryonic cells. These
  can be transcription factors - remember cell
  communication?

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Our friend Drosophila !
Has 3 partshead, thorax, and abdomen has an
anterior/posterior axis and a dorsal/ventral axis
Cytoplasmic determinants and induction together
lead to PATTERN FORMATION
Dorsal
Anterior
Posterior
Ventral
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• Pattern formation is the development of the
• spatial organization of an organism.
• Molecular clues (positional information) tell
  cells
• where theyll be located in the body
• who their neighbors will be
• how to respond to other molecular signals

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Cell Lineage of all 959 C. elegans cells!
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Homeotic genes determine the segment on which
appendages or other structures will form The
expression of these genes is activated
by Transcription factors coded by segmentation
genes.
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All homeotic genes contain a homeobox
domain. Homeobox domains have been found in many
other animals besides flies, and most genes with
a homeobox are related to development. The
homeobox domain is actually a DNA- binding
domain! So proteins containing it are likely to
be transcription factors!!
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Flies and mice have homologous genes coding
for proteins involved in development.
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Induction is when cells signal other cells
to change in a specific waymostly activating or
inactivating transcription. Induction has been
studied most in the nematode, C. elegans.
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Vulva precursor cells can develop into
3 different types of cells. Signals from
the anchor cell induce the determination of
each cell. Effects of inducers can vary
depending on concentration.
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Apoptosis is programmed cell deathoccurs at
various stages of development. Suicide proteins
are activated - cell blebs (becomes multilobed),
nucleus condenses, and then slowly degrades due
to nucleases and proteases.how painful! It is
then eaten by neighboring cells.
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Apoptosis is programmed cell deathoccurs at
various stages of development ex web
retraction between digits/fingers (textbook
activity)
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MUTANT MICE GALLERY!In the name of
Science..Are you ready for the gore?
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Figure 21.x2a Laboratory mice brachyury mutant
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Figure 21.x2b Laboratory mice eye-bleb mutant
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Figure 21.x2c Laboratory mice Hfh11 mutant
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Figure 21.x2d Laboratory mice Lama2 mutant
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Figure 21.x2e Laboratory mice Lepr mutant
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Figure 21.x2f1 Laboratory mice Mgf mutant
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Figure 21.x2f2 Laboratory mice Pax3 mutant
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Figure 21.x2g Laboratory mice Otc mutant
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Figure 21.x2h Laboratory mice Pax6 mutant
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Figure 21.x2i Laboratory mice Pit1 mutant
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Figure 21.x2j Laboratory mice pudgy mutant
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Figure 21.x2k Laboratory mice ruby-eye mutant
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Figure 21.x2l Laboratory mice stargazer mutant
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Figure 21.x2m1 Laboratory mice ulnaless mutant
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Figure 21.x3 Nude mouse
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Figure 21.x4 Normal and double winged Drosophila