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CHAPTER 19
DEVELOPMENTAL
GENETICS
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Development
Refers to a series of changes in the state of the cell, tissue, organ, or organism
Underlying process that gives rise to the structure and function of living organisms
Developmental genetics aimed at understanding how gene expression controls this process
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Sperm and egg unite to produce a zygote That diploid cell divides and develops into the
embryo Cells divide and begin to arrange themselves Each cell becomes determined – destined to
become a particular cell type Commitment occurs before differentiation –
cell’s function and morphology have permanently changed into a highly specialized cell type
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Genome is a set of genes that constitute the program of development
Unicellular organisms – controls structure and function of the single cell
Multicellular – controls cellular features and the arrangement of cells
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Model organisms Fruit fly Drosophila melanogaster
Advanced techniques for generating and analyzing mutants
Large enough for easy study but small enough to determine where genes are expressed
Nematode worm Caenorhabditis elegans Simplicity – only about a thousand somatic cells Pattern of cell division and fate of each cell known
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House mouse Mus musculus Zebrafish Brachydanio rerio Thale cress Arabidopsis thaliana
Wild mustard family Short generation time, small genome
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Pattern formation
Coordination of events leading to the formation of a body with a particular pattern
Formation of an adult body with 3 axesDorsoventral, anteroposterior, and right-leftMay also be segmentedPlant bodies are formed along a root-shoot
axis in a radial pattern
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Positional information Each cell in the body must become the
appropriate cell type based on its relative position
Each cell receives positional information that tells it where to go and what to become
Cell may respond byCell division, cell migration, cell differentiation or
cell death (apoptosis)
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2 main mechanisms used to communicate positional informationMorphogens Cell adhesion
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Morphogens
Give positional information and promote cellular changes
Act in a concentration dependent manner with a critical threshold concentration
Distributed asymmetrically In the oocyte or egg precursor In the embryo by secretion and transport
Induction – cells govern fate of neighboring cells
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Cell adhesion
Each cell makes its own cell adhesion molecules (CAMs)
Positioning of a cell within a multicellular organism is strongly influenced by the combination of contacts it makes with other cells and with the extracellular matrix
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Hierarchy of transcription factors
Four general phases for body formation Organize body along major axes Organize into smaller regions (organs, legs) Cells organize to produce body parts Cells themselves change morphologies and become
differentiated Differential gene regulation – certain genes expressed
at specific phase of development in a particular cell type
Parallel between phases and expression of specific transcription factors
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Animal development
Drosophila model Oocyte establishes pattern for adult
Elongated cell with positional information After fertilization, zygote develops into blastoderm
Series of nuclear divisions without cytoplasmic division (produces many free nuclei) synctial blastoderm
Individual cells are created after nuclei line up along cell membrane (cellular blastoderm)
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Gastrulation involves cells migrating to the interior3 cell layers formed- ectoderm, mesoderm and
endoderm Segmented body plan develops
Head, thorax and abdomen Larva – free living Pupa – undergoes metamorphosis Adult Egg to adult in 10 days
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Phase 1 Pattern development
First phase is establishment of body axes Morphogens are distributed prior to fertilization Bicoid, example morphogen
Mutation results in larva with 2 posterior ends Nurse cells are located near anterior end of oocyte Bicoid gene transcribed in nurse cells and mRNA transported
into anterior end of oocyte Maternal effect Transcription factor that activates particular genes at specific
times Asymmetrical distribution means activated only in certain regions
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Phase 2 Segments Normal Drosophila embryo divided into 15
segments3 head, 3 thoracic and 9 abdominalEach will give rise to unique morphological
features in adult
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Bithorax gene complexNormal – wings on 2nd thoracic segment and 2
halteres on 3rd thoracic segmentMutant – 3rd segment has wings so 2 sets of
wings and no halteres
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3 classes of segmentation genes
Gap genesMutation – several adjacent segments are missing
Pair-rule genesMutation – alternating segments or parts of
segments deleted Segment-polarity genes
Mutation – portions of segments to be missing either anterior or posterior region and adjacent regions to mirror each other
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To create a segment in phase 2, a group of genes acts sequentially to govern the fate of a given body region
Maternal effect genes, which promote phase 1 pattern development, activate gap genes Seen as broad bands of gap gene expression in the embryo
Gap genes and maternal effect genes then activate the pair-rule genes in alternating stripes in the embryo
Once the pair-rule genes are activated, their gene products then regulate the segment-polarity genes
Expression of a segment-polarity gene corresponds to portions of segments in the adult fly
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Phase 3 Segment characteristics Each segment begins to develop its own unique
characteristics Cell fate – ultimate morphological features that
a cell or group of cells will adopt Mutations in homeotic genes alter cell fate
Bithorax is an example of a homeotic mutation Order of homeotic genes along chromosome
corresponds to their expression along the anteroposterior axis of bodyColinearity rule
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Role of homeotic genes to determine identity of particular segments
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Homeotic genes encode homeotic proteins that functionas transcription factors Activate transcription of
specific genes that promote developmental changes
Homeobox – coding sequence of homeotic genes contains 180-bp sequence Encodes homeodomain for
DNA binding
A Homologous Group of Homeotic Genes Is Found in All Animals
Identify vertebrate genes that are homologous to those that control development in simpler organisms such as DrosophilaHybridization techniques
Homologous genes are evolutionarily derived from the same ancestral gene and have similar DNA sequences
Hox genes in miceFollow colinearity ruleKey role in patterning anteroposterior axis
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Phase 4 Cell differentiation
Emphasis shifts to cell differentiation Studied in mammalian cell culture lines Differential gene expression underlies cell
differentiation Stem cell characteristics
Capacity to divideDaughter cells can differentiate into 1 or more cell
types
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Stem cell categories
TotipotentUltimate stem cell is fertilized eggCan produce all adult cell types
PluripotentEmbryonic stem cells (ES cells)Embryonic germ cells (EG cells)Can differentiate into almost any cell but a
single cell has lost the ability to produce an entire individual
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MultipotentCan differentiate far fewer types of cellsHematopoietic stem cells (HScs)
UnipotentDaughter cells become only one cell typeStem cells in testis produce only sperm
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Robert Davis, Harold Weintraub, and AndrewLasser Identified Genes Encoding TranscriptionFactors That Promote Muscle Cell Differentiation
What causes stem cells to differentiate into a particular cell type?
Certain proteins function as “master transcription factors”
Initial experimental strategy to identify genes expressed only in differentiating muscle cells
Narrowed down to 3 genes Would any of these 3 genes cause nonmuscle cells to
differentiate into muscle cells?
MyoD was the only one to cause fibroblasts to differentiate into muscle cells
Belongs to myogenic bHLH genes Found in all vertebrates and activated during skeletal muscle
development Features promoting muscle cell differentiation
Basic domain binds specifically to an enhancer DNA sequence that is adjacent to genes that are expressed only in muscle cells
Protein contains an activation domain that stimulates the ability of RNA polymerase to initiate transcription
Interacts with other cellular proteins Id – prevents muscle differentiation too soon E – activates gene expression
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Plant development 2 key features of complex plant morphology
Root-shoot axisRadial pattern
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Differs from animal developmentNo cell migrationNo morphogensAn entirely new individual can be regenerated
from somatic cells (totipotent) Similarities to animal development
Use differential gene expressionUse of transcription factors
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Arabidopsis model for development After fertilization, the first cellular division is
asymmetrical and produces a smaller apical cell and a larger basal cell Apical cell – gives rise to most of embryo and shoot Basal cell – root and suspensor cell for seed
formation Heart stage – about 100 cells
Basic organization established Root meristem – gives rise only to root Shoot meristem – all aerial parts of plant – stem,
leaves, flowers 2 cotyledons to store nutrients
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Seedling3 main regions
Apical region – leaves and flowers
Central region – stem Basal region – roots
Shoot meristem organizing center
Central zone – maintains undifferentiated stem cells
Peripheral zone – dividing cells that will differentiate
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Apical, central and basal regions express different sets of genes
Apical-basal patterning genes
Defects can cause dramatic effects
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Plant homeotic genes
First known homeotic genes discovered in plants
Normal Arabidopsis flower composed of 4 concentric whorls
1. Sepals – outer whorl, protects bud2. Petals3. Stamens – make pollen (male gametophyte)4. Carpel – produces female gametophyte
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ABC model for flower development3 gene classes A, B, C and EWhorl 1 – gene A product = sepalsWhorl 2 – gene A, B and E products = petalsWhorl 3 – gene B, C and E products =
stamensWhorl 4 – gene C and E products = carpel
Leaf structure is default pathway If A,B,C and E are defective, leaves result
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