7. Anteriorposterior patterning
Goals
Overview
- Maternal and segmentation genes revisited
- The body plan and homeotic genes
- Homeotic transformations: change of developmental fate
- The Lewis model
- Cloning Antennapedia: understanding the molecular basis
- Drosophila Hox genes are organized in two clusters
- The homeobox encodes the homeodomain
- The homeodomain: an evolutionarily ancient and highly conserved DNA-binding domain
- Colinear Hox gene expression
- Hox genes in other species – vertebrates and mammals
- Hox genes: limb patterning – medical relevance
- Hox genes: a model to study evolution
- A case study: changing limb numbers in Arthropods
How is developmental fate along the anteriorposterior axis
determined? Hox genes: a Swiss army knife for development and
evolution
How is each segment distinguished from the next segment?
Hox genes were first defined and
identified in drosophila
previous class:
- Anterior and posterior
determinants: bicoid and
nanos which have
localized mRNA which
become proteins and form
an opposing gradient.
- These gradients are then
subsequently converted
into increasingly defined
expression patterns of the 3 categories of segmentation genes:
- Gap genes / Pair-rule genes / segment polarity genes.
1
, We know how to make segments, but we don’t know how each segment is gaining its identity!
Maternal, gap, and pair-rule genes
revisited
Distribution of proteins in gradients.
- Bicoid and hunchback were transcriptional
activators to regulate this pair-rule gene, eve
stripe 2
- Gaint and Krüppel are both repressors
Consequence the activators lead to stimulate
expression of evenskipped in this particular
stripe, and the repressors restrict it to that stripe.
Alternating expression of even-
skipped and fushi tarazu, 2 pair-rule
genes. In the protein distribution they
are always separated by a single line
of cells where neither even-skipped
nor fushi tarazu is expressed. Exactly
at that location wingless (an important segmentpolarity gene) is first expressed. So even-skipped and
fushi tarazu are negative regulators of wingless.
Wingless is secreted it will stimulate expression of engrailed in the neighbouring cell. Engrailed in turn
will regulate expression of hedgehog which is a secreted molecule again.
- Wingless: paracrine
- Hedghog: gradient
How do we give each of those segments their identity?! homeotic genes!
First discovered in the body plan.
Homeotic transformation = change of developmental fate where a structure is replaced by a copy of a
structure which is normally elsewhere in the body.
- Antennapedia
- Bithorax on second thoracic segment normally wings are present, on third thoracic
segment they have a pair of halters. Here the third thoracic segment is replaced by a copy of
the second thoracic segment, resulting in 4 wings.
This type of variations of the posterior parts of the drosophila were studied by Ed Lewis The Lewis
model.
Based on a collection of homeotic mutations he came up with a
model, that could explain what he observed.
- The second thoracic segment as the ground state to all
more posterior segments.
2
Goals
Overview
- Maternal and segmentation genes revisited
- The body plan and homeotic genes
- Homeotic transformations: change of developmental fate
- The Lewis model
- Cloning Antennapedia: understanding the molecular basis
- Drosophila Hox genes are organized in two clusters
- The homeobox encodes the homeodomain
- The homeodomain: an evolutionarily ancient and highly conserved DNA-binding domain
- Colinear Hox gene expression
- Hox genes in other species – vertebrates and mammals
- Hox genes: limb patterning – medical relevance
- Hox genes: a model to study evolution
- A case study: changing limb numbers in Arthropods
How is developmental fate along the anteriorposterior axis
determined? Hox genes: a Swiss army knife for development and
evolution
How is each segment distinguished from the next segment?
Hox genes were first defined and
identified in drosophila
previous class:
- Anterior and posterior
determinants: bicoid and
nanos which have
localized mRNA which
become proteins and form
an opposing gradient.
- These gradients are then
subsequently converted
into increasingly defined
expression patterns of the 3 categories of segmentation genes:
- Gap genes / Pair-rule genes / segment polarity genes.
1
, We know how to make segments, but we don’t know how each segment is gaining its identity!
Maternal, gap, and pair-rule genes
revisited
Distribution of proteins in gradients.
- Bicoid and hunchback were transcriptional
activators to regulate this pair-rule gene, eve
stripe 2
- Gaint and Krüppel are both repressors
Consequence the activators lead to stimulate
expression of evenskipped in this particular
stripe, and the repressors restrict it to that stripe.
Alternating expression of even-
skipped and fushi tarazu, 2 pair-rule
genes. In the protein distribution they
are always separated by a single line
of cells where neither even-skipped
nor fushi tarazu is expressed. Exactly
at that location wingless (an important segmentpolarity gene) is first expressed. So even-skipped and
fushi tarazu are negative regulators of wingless.
Wingless is secreted it will stimulate expression of engrailed in the neighbouring cell. Engrailed in turn
will regulate expression of hedgehog which is a secreted molecule again.
- Wingless: paracrine
- Hedghog: gradient
How do we give each of those segments their identity?! homeotic genes!
First discovered in the body plan.
Homeotic transformation = change of developmental fate where a structure is replaced by a copy of a
structure which is normally elsewhere in the body.
- Antennapedia
- Bithorax on second thoracic segment normally wings are present, on third thoracic
segment they have a pair of halters. Here the third thoracic segment is replaced by a copy of
the second thoracic segment, resulting in 4 wings.
This type of variations of the posterior parts of the drosophila were studied by Ed Lewis The Lewis
model.
Based on a collection of homeotic mutations he came up with a
model, that could explain what he observed.
- The second thoracic segment as the ground state to all
more posterior segments.
2
