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Developmental Genetics
How Selective Gene Expression
Determines the Developmental
Fate of Specific Cells
-Chapter 17, pages 461-463
-Chapter 22, pages 599-609
Definitions
• Determination = process of commitment
of a cell to a particular fate
• Differentiation = changes in cell shape
and physiology associated with
production of final cell type
• Developmental field = a set of cells that
together interact to form a developing
structure
• Morphogen = substance that specifies
cell identity as a function of its
concentration
Gene Expression
• Differentiation depends upon the
expression of a specific subset of genes.
• Gene expression can be controlled at
any level between transcription and
activation of the protein product.
Control Points for
Gene Expression in Eukaryotes
DNA
Transcriptional Control
transcription
RNA
Post-Transcriptional Control
processing
Translational Control
translation
Protein
Post-Translational Control
Developmental “Decisions”
• Binary decisions
Separation of germ line from soma
Establishment of gender*
• Choosing one fate from multiple options
Axis formation*
Segmentation*
Germ layer formation
Organogenesis
Ratio of Sex Chromosomes
to Autosomes (X:A)
Balance of Active
Transcription Factors
Presence or Absence
Of Sxl Protein
Sxl Protein Regulates
Splicing of tra mRNA
Tra Protein Regulates
Splicing of Dsx mRNA
A Cascade of Events Affects
Expression of Sex-specific
Traits in Drosophila
Sxl Protein Regulates
Splicing of its own mRNA
Tra Proteins Regulate
Splicing of fru mRNA
Dsx Proteins Activate
or Repress Transcription
of Sex-Specific Genes
Fru Proteins
Control
Sex-Specific
Behavior
Effects of X:Autosome Ratio
Transcriptional Regulation As a
Result of X:Autosome Ratio
NUM:NUM dimers
activate
transcription of
Sxl gene
Post-transcriptional Regulation
of Sxl Protein Production
Post-transcriptional Regulation of
Tra and Fru Protein Production
Sxl Protein Regulates
Splicing of tra mRNA
Post-transcriptional Regulation:
Alternative Splicing of Tra pre-mRNA
Sxl protein may
block upstream
3’ splice site
Post-transcriptional Regulation of
Fru Protein Production
Sxl Protein Regulates
Splicing of tra mRNA
Tra Proteins Regulate
Splicing of fru mRNA
Nervous system
processing of
information from
antennae
Courtship Song
Abdomen Movement
Fru Proteins
Control
Sex-Specific
Behavior as
Transcriptional
Regulators
Post-Transcriptional Regulation of DSX
Protein Production
Tra Protein Regulates
Splicing of Dsx mRNA
Dsx Proteins Activate
or Repress Transcription
of Sex-Specific Genes
Summary of Protein Activities
NUM:NUM
Homodimers
NUM = numerator
Sxl = Sex Lethal
Tra = Transformer
Dsx = Double sex
Fru = Fruitless
Development of AnteriorPosterior Body Axis in Drosophila
A Hierarchy of Gene Interactions Determines
Segment Number and Identity Along the A-P Axis
Egg-polarity genes
(Maternal)
Gap genes
Pair-rule genes
Segment-polarity genes
Homeotic genes
Distribution of Egg-polarity Gene Products
Action of Egg-polarity Genes Bicoid and Nanos
Bicoid antpost Transcriptional activator of anteriorspecific genes, including hunchback, a
gene needed of head and thorax
development
Nanos postant Translational repressor of hunchback,
preventing expression of anterior
structures
Genes Influencing Segmentation along the A-P Axis
Action of Gap Genes
Gap gene products divide the body
into broad zones for the formation
of anteriorposterior segments.
Mutations show a loss of specific
adjacent segments from the region
where a gap gene is transcribed.
Krupple and Knirps encode
transcription factors.
Action of Pair-Rule Genes
Pair-rule genes divide
the body into a series of
two-segment units.
Pair-rule gene mutations
remove alternate
segments, either odd or
even.
Alternating activity of the
genes Ftz (stained gray) and
Eve (stained brown) is shown.
Fushi tarazu (Ftz) and
Even-skipped (Eve)
encode transcription factors.
Action of Segment-Polarity Genes
Segment-polarity genes
regulate the organization
of subsets of cells within
a segment.
Segment-polarity
mutations cause part of a
segment to be deleted
and replaced by a mirror
image of a different part
of the next segment.
Engrailed (EN) encodes a
transcription factor.
Patched encodes a
transmembrane protein.
Action of Homeotic Genes
Homeotic genes influence the
identity of specific segments,
controlling the development of
segment-specific structures.
Mutations cause structures from
one segment to develop in
another.
T3 develops as T2 in the Postbithorax
mutation.
Pbx is a cis-regulatory region controlling
the action of Ubx on T3 development.
Clusters of
Homeotic Genes
Cluster
Affects Structures
Developing in
Genes
Antennapedia
Complex
Head and Anterior
Thoracic Regions
Antennapedia
Scr
Bithorax
Complex
Abdomen and
Posterior Thoracic
Regions
Ultrabithorax
Abdominal-A
Abdominal-B
Scr
Ubx
Antp
Abd-B
Evidence for the correspondence between gene order and
sequence of gene expression for the homeotic genes.
Evolutionary Conservation of Homeotic Gene Regions
• Homeotic genes share a 180 base pair
region called the homeobox.
• The homeobox encodes a DNA-binding
domain (homeodomain) with a
helix-turn-helix structural motif.
• Homeobox regions are found in
clustered genes in the mouse.
Homeotic gene mutation resulting in
posterior location for anterior structures,
i.e. ribs from lumbar vertebrae.