Transcript Ch. 12: Presentation Slides

11
The Genetic Control of
Development
Genes and Development
• The genotype determines not only the events that
take place in development but also the temporal
order in which the events unfold
• Key process in development is pattern formation,
which means emergence of spatially organized and
specialized cells in the embryo from cell division
and differentiation of the fertilized egg
• Genetic analyses of development often make use of
mutations that alter developmental patterns
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Development: Transcriptional Control
• S. cerevisiae, has two mating types denoted a and 
• The specific mating type of a cell is controlled at the
level of transcription
• The alternative mating-type alleles MATa (mating
type a) and MAT (mating type  ) both express a set
of haploid-specific genes, including HO for the HO
endonuclease used in mating-type interconversion,
and RME1 for a repressor of meiosis-specific genes.
• MATa also expresses a set of a-specific genes and
MAT expresses a set of -specific genes.
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Development: Transcriptional Control
• Expression of genes that differ in the mating types
include
 secretion of a mating peptide, and
 production of a receptor for the mating peptide secreted by the
opposite mating type
• Therefore, when a and  cells are in proximity, they
prepare each other for mating and undergo fusion
• In a cell of mating type a, the MATa region is
transcribed and a polypeptide called a1 is produced
• a1 alone is inactive regulator, and in the absence of
any regulatory signal, asg (a-specific genes) and hsg
(haploid-specific genes) are transcribed, but sg (specific genes ) are not
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Development: Transcriptional Control
• In a cell of mating type , the MAT region is
transcribed, and proteins 1 and 2 are produced: 1
is a positive regulator of the -specific genes, and 2
is a negative regulator of the a-specific genes
• The result is that sg and hsg are transcribed, but
transcription of asg is turned off.
• In the diploid both MATa and MAT are transcribed, but
the only polypeptides produced are a1 and 2
• The reason is that the a1 and 2 combine to form a
negative regulator of the 1 gene in MAT and of the
hsg
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Development: Transcriptional Control
• The 2 polypeptide acting alone is a negative
regulatory protein that turns off asg
• Because 1 is not produced, transcription of sg is
not turned on
• The overall result is that the sg are not turned on
because 1 is absent, the asg are turned off because
2 is present, and the hsg are turned off by the a1/2
complex
• This ensures that meiosis can occur (RME1 is turned
off) and that mating-type switching ceases (the HO
endonuclease is absent).
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Fig. 11.1
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Caenorhabditis elegans
• Nematodes are diploid organisms with two sexes
• In C. elegans, the two sexes are the hermaphrodite
and the male
• The hermaphrodite contains two X chromosomes
(XX), produces both functional eggs and functional
sperm, and is capable of self-fertilization
• The male produces only sperm and fertilizes the
hermaphrodites
• There is no Y chromosome, and the male karyotype
is XO
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Caenorhabditis elegans
• Nematode development is unusual: the pattern of cell
division and differentiation is virtually identical from
one individual to the next
• As a result each sex shows the same geometry in the
number and arrangement of somatic cells
• The hermaphrodite contains exactly 959 somatic
cells, and the male contains exactly 1031 somatic
cells
• The complete developmental history of each somatic
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cell is known
Genetic Control of Cell Lineages
• Lineage of a cell is ancestordescendant relationships among
a group of cells
• Lineage diagram is a sort of cell
pedigree that shows each cell
division and indicates the
terminal differentiated state of
each cell
• Cell fate is determined by
autonomous development and/or
intercellular signaling.
Fig. 11.3
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Gene Regulation in Development
• Cell fate is progressively restricted in animal
development
• Cell fate = developmental outcome of cells within
a lineage
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Gene Regulation in Development
• Two principal mechanisms progressively restrict
the cell:
 Developmental restriction may be autonomous, which
means that it is determined by genetically programmed
changes in the cells themselves
 Cells also may respond to positional information, which
means that developmental restrictions are imposed by the
position of cells within the embryo
Positional information may be mediated by signaling
interactions between neighboring cells or by gradients in
concentration of particular molecules.
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Genes and Development
• Many mutations studied in nematodes reveal several
general features by which genes control
development:
• The division pattern and fate of a cell are generally
affected by more than one gene
• Most genes that affect development are active in
more than one type of cell
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Genes and Development
• Complex lineages often include simpler,
genetically determined sublineages within them
• The lineage of a cell may be triggered
autonomously within the cell itself or by signaling
interactions with other cells
• Regulation of development is controlled by genes
that determine the different sublineages that cells
can undergo and the individual steps within each
sublineage.
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Genes and Cell Fate
• Genes that control cell fate can be identified by the
unusual property: dominant and recessive
mutations have opposite effects
• If alternative alleles of a gene result in opposite cell
fates, then the product of the gene must be both
necessary and sufficient for expression of the fate
• Recessive mutations often result from loss of
function—the mRNA is not produced or the protein
is inactive
• Dominant mutations often result from gain of
function—the gene is overexpressed or is
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expressed at the wrong time
Lineage Mutations
• In C. elegans, a relatively small number of genes
have dominant and recessive alleles that affect
the same cells in opposite ways
• Among them is the lin-12 gene, which controls
developmental decisions in a number of cells
• The molecular structure of the lin-12 gene product
is typical of a transmembrane receptor protein
containing regions that span the cell membrane
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Fig. 11.5
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Lineage Mutations
• Cells can determine the fate of other cells through
ligands that bind with their transmembrane
receptors
• lin-3 expressed in anchor cell controls the fate of
other cells in the development of the vulva
• Loss of LIN-3 results in the complete absence of
vulval development, whereas overexpression of
LIN-3 results in excess vulval induction.
• LIN-3 is a typical example of an interacting
molecule, or ligand, that binds with an EGF-type
transmembrane receptor
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Fig. 11.7
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Development of Drosophila
• Development in Drosophila illustrates progressive
regionalization and specification of cell fate
• Early development in Drosophila takes place within
the egg case
• The first nine mitotic divisions occur rapidly
without division of the cytoplasm and produce a
cluster of nuclei within the egg (syncytium)
• Some nuclei migrate to the periphery of the embryo
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Development of
Drosophila
• At the posterior end, the
pole cells (which form the
germ line) become
cellularized
• Additional mitotic divisions
occur within the syncytial
blastoderm
• Membranes are formed
around the nuclei, giving
rise to the cellular
blastoderm
Fig. 11.10
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Genes in Pattern Formation
• Cells in the blastoderm have predetermined
developmental fates, with little ability to substitute
for other, sometimes even adjacent, cells
• The earliest stages of Drosophila development are
programmed in the oocyte
• Mutations that affect oocyte composition or
structure can upset development of the embryo
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Genes in Pattern Formation
• Genes that function in the mother that are needed
for development of the embryo are called maternaleffect genes
• Developmental genes that function in the embryo
are called zygotic genes
• The zygotic genes interpret and respond to the
positional information laid out in the egg by the
maternal-effect genes.
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Genes in Pattern Formation
• Drosophila embryo and larva have segmental
organization
• The segments are defined by successive
indentations formed by the sites of muscle
attachment in the larval cuticle
• The parasegments are not apparent
morphologically but include the anterior and
posterior regions of adjacent segments
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Genes in Pattern Formation
• The early stages of pattern formation are
determined by segmentation genes
• There are four classes of segmentation genes
that differ in their times and patterns of
expression in the embryo:
1. coordinate
2. gap
3. pair-rule
4. segment-polarity
• The coordinate genes determine the anterior–
posterior and dorsal–ventral axis of the embryo
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Genes in Pattern Formation
• The gap genes are expressed in contiguous groups
of segments along the embryo and establish the
next level of spatial organization. Mutations in gap
genes result in the gaps in the normal pattern of
structures in the embryo
• The pair-rule genes determine the separation of the
embryo into discrete segments. Mutations in pairrule genes result in missing pattern elements in
alternate segments
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Genes in Pattern Formation
• The segment-polarity genes determine the pattern
of anterior–posterior development within each
segment of the embryo. Mutations in segmentpolarity genes affect all segments or parasegments
in which the normal gene is active
• Interactions among genes in the regulatory
hierarchy ensure an orderly progression of
developmental events
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Fig. 11.12
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Homeotic Genes
• As with many other insects, the larvae and adults of
Drosophila have a segmented body plan
• The metamorphosis of the adult makes use of about
20 structures called imaginal disks present inside
the larvae
• Formed early in development, the imaginal disks
give rise to the principal structures and tissues in
the adult organism
• Among the genes that transform the periodicity of
the Drosophila embryo into adult body plan are two
small sets of homeotic, or HOX, genes.
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Homeotic Genes
• Mutations in homeotic genes result in the
transformation of one body segment into another
• Most HOX genes contain one or more copies of a
characteristic sequence of about 180 nucleotides
called a homeobox
• Homeobox is highly conserved in evolution
• Homeotic genes are transcriptional regulators
• HOX genes function at many levels in the
regulatory hierarchy
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Fig. 11.18
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Plant Development
• Floral development in Arabidopsis illustrates
combinatorial control of gene expression
• In higher plants, differentiation takes place almost
continuously throughout life in regions of actively
dividing cells called meristems in both the
vegetative organs and the floral organs
• As groups of cells leave the proliferating region of
the meristem and undergo further differentiation,
their developmental fate is determined almost
entirely by their position relative to neighboring
cells.
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Plant Development
• The flowers of Arabidopsis are composed of four types of
organs arranged in concentric rings, or whorls. Each whorl
gives rise to a different floral organ:
•
•
•
•
whorl 1 yields the sepals,
whorl 2 the petals,
whorl 3 the stamens,
whorl 4 the carpels
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Fig. 11.24
Plant Development
• Mutations that affect floral development fall into
three major classes, each with a characteristic
phenotype:
 The phenotype lacking sepals and petals is caused by
mutations in the gene ap1 (apetala-1)
 The phenotype lacking stamens and petals is caused by a
mutation in either of two genes, ap3 (apetala-3) or pi
(pistillata)
 The phenotype lacking stamens and carpels is caused by
mutations in the gene ag (agamous)
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Plant Development
• ap1, ap3, pi and ag encode transcription factors
that are members of the MADS box family of
transcription factors
• MADS box transcription factors include a common
sequence motif consisting of 58 amino acids, and
they are involved frequently in transcriptional
regulation in plants and to a lesser extent in
animals
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Table 11.1
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Plant
Development
• Flower development in
Arabidopsis is controlled
by the combination of
genes expressed in each
concentric whorl
• The developmental identity
of each concentric ring is
determined by ap1, ap3, pi,
and ag, each of which is
expressed in two adjacent
rings
• Therefore, each whorl has
a unique combination
of active genes
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Fig. 11.26
Programmed Cell Death
• Programmed cell death (PCD) occurs in
developmental pathways
• PCD or apoptosis is a form of cell suicide that
removes specific cells as part of pattern
formation
• Mutations in cell death genes may cause tissue
malformations or abnormal cell growth patterns
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