L20: Pattern Formation of Drosophila Flashcards
what are the two differences in early embryo patterning mechanisms?
- egg fertilization - egg polarity (fly egg is highly polar where as a mouse/human egg is nonpolar)
- Early embryo - most animals go through cleavage divsions but the fly goes through syncytium
why do we care about Drosophila development?
-short generation time - 9 days to sexual maturity
-sophisticated genetic and molecular biology tools
-studies in drosophila have revealed how genetic control mechanisms govern development
-many basic mechanisms, including the functions of specific molecules (Hox genes), are conserved in humans
fate map of fly development
questions:
* How does this segmented pattern forms?
* How does each segment know its identity?
* How is the pattern maintained throughout development?
approach: genetic screens (looking for mutants with defects)
drosophila early embryo is a syncytium
- unfertilized fly egg is already polarized
- fertilized egg
- many nuclei divide rapidly in a syncytium
- nuclei migrate to periphery, where cell boundaries will eventually form
- 13 divisions prior to cellularization, forms multiple somatic cells
bristle patterns reveal…
distinct anterior-posterior (A-P) difference among and within segments
egg-polarity gene (bicoid)
missing anterior or posterior segments
what are the three segmentation genes?
- gap gene - missing several contiguous segments
- pair-rule gene - missing alternating segments
- segment-polarity gene - polarity defect in every segment
hierarchy of gene regulatory interaction patterns
first, egg polarity genes organize the A-P axis of early embryo (prior to fertilization)
this affects expression of three groups of genes which control segmentation along A-P axis: gapm pair-rule, seegment-polarity genes
hox genes…
give identity to each segment
egg polarity genes…
encode maternal molecules deposited in the egg
bicoid mutants lack anterior
segments
- Maternal bicoid mRNA is localized
to the anterior of the egg prior to
fertilization - Bicoid protein is made after
fertilization and diffuses in the
syncytium, forming a gradient
from anterior to posterior - Bicoid is a transcription regulator
- Bicoid regulates the expression of
gap and pair-rule genes - Bicoid acts as a morphogen!
Activates expression of genes in a
concentration-dependent manne
egg-polarity gene products form opposing gradients
egg polarity gene product gradients induce epression of zygotic genes and turn on —– genes
GAP genes
gap genes are…
- Expressed in broad domains (multiple segments)
- Encode transcription regulators
- Their expression is regulated by
egg-polarity genes - They regulate the expression of
other gap genes and pair-rule genes
pair-rule genes…
- Mutants lack every other segment
(either odd or even segments
depending on the gene) - Expressed in 7 segments (either
even or odd) ~ or 7 ‘stripes’ - Encode transcription factors
- Their expression is regulated by
gap genes and egg-polarity genes - They regulate the expression of
other pair-rule genes and
segment-polarity genes
how to determine which factors regulate the expression of a gene?
example: Gene A
pair rule genes….
*Mutants lack every other segment
(either odd or even segments
depending on the gene)
- Expressed in 7 segments (either
even or odd) - Encode transcription factors
- Their expression is regulated by
gap genes and egg-polarity genes - They regulate the expression of
other pair-rule genes and
segment-polarity gene
how do segment polarity genes differ from the other three types of genes?
they maintain their expression through development
encode transcription factors and signaling pathway components
other three gene types remain inmemory of cells but do not remain expressed, only transiently expressed
a signaling loop maintains expression of segment polarity genes
Engrailed, Wingless and Hedgehog, are segment polarity genes expressed at posterior end of each
segment in neighboring cells
- Engrailed = transcription factor; Wingless and Hedgehog are secreted proteins and paracrine
signaling molecules - MUTUALLY REINFORCING SIGNALS between Wingless expressing cells and Hedgehog expressing
cells maintains the narrow stripes of expression (cell memory) throughout development
when are each type of gene expressed in terms of the fly cell cycle of development
how do the segments know their identity (i.e. what they should become?)
hox genes
expression pattern and function of Hox proteins
Hox proteins are….
-transcription regulators that bind to DNAA through their homeodomains
-act as master regulators by controlling the expression of multiple genes
hox gene is maintained in adults, occurs via…
Hox gene expression must be maintained
throughout development
This occurs via epigenetic inheritance of
histone modifications & recruitment of
chromatin remodeling complexes
The Hox genes are present and play a role in
anterior-posterior patterning in all bilaterally
symmetric animals, including vertebrates
first molecular evidence that development of all animals was based on common principles and molecular mechanisms
Hox genes regulate limb development in vertebrates
mutations of different Hox genes will result in malformations of specific regions of the limb (S, Z, A regions)
what are paralogs
similar gene sequences that have similar expression patterns
