Homeotic genes and segmentation in vertebrate and other invertebrate
Learning objective:
1. Homeodomain protein determine the identity of individual segments along the A-P axis.
2. Homeodomain proteins determine regional identity in developing limbs along the A-P and proximal-distal axis
3. Notch signalling is required for segmentation in vertebrates and other invertebrates
Background information
• Homeobox genes are sometimes called hox genes
• Hox genes are found in all organism
• Hox genes are found in clusters called Hox clusters
• Homeobox is found within the cluster of homeobox genes that codes for a protein that regulates the gox cluster
• Homeotic selector genes, homeodomain protein,…etc in shot are all known as hox genes
• Hox genes regulate the development of anatomical structures in various organisms, such insects, mammals and plants
Homeotic genes
• Drosophila and other animals are segmented of whole body plan
- i.e. head segment, Thoracic segment, abdominal segment
• Once divided into segments, how does head cells know they are in the head segment?
- Homeotic genes
- This question can be asked for any segment
Homeodomain proteins are transcription factors
• The homeodomain or homeobox is encoded by a 180 bp DNA sequence
• The homeobox folds into 3 α-helices
• Helix 3 binds DNA
Part of the homeobox are conserved in all homeodomain proteins
• Homeobox gene encodes homeobox protein
• Homeobox
- Large family of similar genes that direct the formation of many body structures during early embryonic development
- Homeodomain protein (transcription factor) binds to genes in the homeobox.
• Enhancers have transcription factor binding sites
• Transcription binding sites have specific DNA sequence because only bind to specific transcription factors
• A 4 base pair motif TAAT is conserved (not disrupted) in nearly all sites recognised by homeodomain.
• HOX transcription factors bind to TAAT sequence
• Gene express results in different cell types.
- Gene expression is controlled by transcription factors (homeodomain)
,All homeodomain binding is destroyed if the first T is mutated
• The base pair following the TAAT motif determine which homeodomain protein recognises the DNA binding site
• If base pair T is mutated with G, C, A then Hox transcription factor cannot bind to TAAT sequence.
• The base pairs following the TAAT motif determine which homeodomain protein recognises the DNA binding site
In individual homeodomain proteins, specific amino acids recognise characteristic base pairs in the DNA binding site
• The lysine of the Bicoid homeodomain pairs with the CG base pair in the DNA binding site.
• Antennapedia, another homeodomain protein binds with the glutamine of the Ant homeodomain to the TA base pair of the
DNA binding site.
• If the lysine in Bicoid is replaced by glutamine, the resulting protein will recognise Antennapedia-binding sites.
The Homeotic Selector Genes (or HOX genes)
• The HOX genes in Drosophila are determine the identity of the individual segments along the anterior-posterior axis.
Segmentation Cascade
• Homeotic genes act in parallel to the segment polarity genes.
- Therefore, when segment polarity genes are activated so are segment polarity genes.
, Homeotic Selector genes are arranged in 2 gene complexes
• In drosophila there are 2 complexes:
- Complex 1: Antennapedia complex (anterior complex)
- Complex 2: bithorax complex (posterior complex)
- Both complexes together are called homeotic complex.
• The genes are arranged on the chromosome in the same way as they are expressed in the embryo along the anterior-
posterior axis.
• Abd = abdominal
Gap and pair-rule genes set up the initial domains of homeotic gene expression
• The hox genes are activated or repressed by gap and pair-rule genes
• The expression of AbdA and AbdB is repressed by Hb and Kr, which prevents these genes from being expressed in the head
and thorax.
• On the other hand, antennapedia is activated by particular levels of Hb so that it is expressed in the second thoracic
segment.
Learning objective:
1. Homeodomain protein determine the identity of individual segments along the A-P axis.
2. Homeodomain proteins determine regional identity in developing limbs along the A-P and proximal-distal axis
3. Notch signalling is required for segmentation in vertebrates and other invertebrates
Background information
• Homeobox genes are sometimes called hox genes
• Hox genes are found in all organism
• Hox genes are found in clusters called Hox clusters
• Homeobox is found within the cluster of homeobox genes that codes for a protein that regulates the gox cluster
• Homeotic selector genes, homeodomain protein,…etc in shot are all known as hox genes
• Hox genes regulate the development of anatomical structures in various organisms, such insects, mammals and plants
Homeotic genes
• Drosophila and other animals are segmented of whole body plan
- i.e. head segment, Thoracic segment, abdominal segment
• Once divided into segments, how does head cells know they are in the head segment?
- Homeotic genes
- This question can be asked for any segment
Homeodomain proteins are transcription factors
• The homeodomain or homeobox is encoded by a 180 bp DNA sequence
• The homeobox folds into 3 α-helices
• Helix 3 binds DNA
Part of the homeobox are conserved in all homeodomain proteins
• Homeobox gene encodes homeobox protein
• Homeobox
- Large family of similar genes that direct the formation of many body structures during early embryonic development
- Homeodomain protein (transcription factor) binds to genes in the homeobox.
• Enhancers have transcription factor binding sites
• Transcription binding sites have specific DNA sequence because only bind to specific transcription factors
• A 4 base pair motif TAAT is conserved (not disrupted) in nearly all sites recognised by homeodomain.
• HOX transcription factors bind to TAAT sequence
• Gene express results in different cell types.
- Gene expression is controlled by transcription factors (homeodomain)
,All homeodomain binding is destroyed if the first T is mutated
• The base pair following the TAAT motif determine which homeodomain protein recognises the DNA binding site
• If base pair T is mutated with G, C, A then Hox transcription factor cannot bind to TAAT sequence.
• The base pairs following the TAAT motif determine which homeodomain protein recognises the DNA binding site
In individual homeodomain proteins, specific amino acids recognise characteristic base pairs in the DNA binding site
• The lysine of the Bicoid homeodomain pairs with the CG base pair in the DNA binding site.
• Antennapedia, another homeodomain protein binds with the glutamine of the Ant homeodomain to the TA base pair of the
DNA binding site.
• If the lysine in Bicoid is replaced by glutamine, the resulting protein will recognise Antennapedia-binding sites.
The Homeotic Selector Genes (or HOX genes)
• The HOX genes in Drosophila are determine the identity of the individual segments along the anterior-posterior axis.
Segmentation Cascade
• Homeotic genes act in parallel to the segment polarity genes.
- Therefore, when segment polarity genes are activated so are segment polarity genes.
, Homeotic Selector genes are arranged in 2 gene complexes
• In drosophila there are 2 complexes:
- Complex 1: Antennapedia complex (anterior complex)
- Complex 2: bithorax complex (posterior complex)
- Both complexes together are called homeotic complex.
• The genes are arranged on the chromosome in the same way as they are expressed in the embryo along the anterior-
posterior axis.
• Abd = abdominal
Gap and pair-rule genes set up the initial domains of homeotic gene expression
• The hox genes are activated or repressed by gap and pair-rule genes
• The expression of AbdA and AbdB is repressed by Hb and Kr, which prevents these genes from being expressed in the head
and thorax.
• On the other hand, antennapedia is activated by particular levels of Hb so that it is expressed in the second thoracic
segment.
