Lecture 4 (2a) Homeodomain Proteins & Hox Genes Flashcards
Homeodomain proteins
- determine the identity of individual segments along the anterior-posterior body axis
- determine regional identity in developing limbs along the anterior-posterior and proximal-distal axis
- determine regional identity in developing nervous system along the dorso-ventral axis
- every segment is different
- during segmentation given identity
Homeodomain proteins are
transcription factors
• must recognize portion of domain
homeodomain coded by a 180-base-pair DNA sequence known as the
homeobox
Homeodomain folds into
3 α-helices
Helix _ binds DNA
3
Parts of the homeobox
are conserved in all homeodomain proteins
A four base pair motif … is conserved in nearly all sites recognized by homeodomains
TAAT is conserved
All homeodomain binding is destroyed if
the first T is mutated
The base pairs following the TAAT motif determine
which homeodomain protein recognizes the DNA binding site
TAAT / specific
general) (eg boicoid GC) (eg ANTP TA
In individual homeodomain proteins specific amino acids
recognize the base pairs in the DNA binding site
Morphologically visible segments and identity appear
at the same time
Homeotic selector genes in Drosophila are
homeodomain proteins that determine the identity of the individual segments along the anterior-posterior axis
Homeotic selector genes are arranged in
2 gene complexes
• antennapedia complex
• bithorax complex
(on chromosome same as expressed in embryo)
Gap and pair-rule genes set up the
initial domains of the homeotic gene
Homeotic selector genes are expressed in
a parasegmental pattern
The expression of a homeotic gene is repressed by
all homeotic gene products expressed posterior to it
TURNS INTO ONE ANTERIOR TO IT ALWAYS
Homeotic mutations result in
transformations
Ubx mutant
2 pairs of wings
• 3rd T segment turns into 2nd T segment
If the bithorax complex is missing
all segments are transformed into the 2nd thoracic segment
Posterior abdominal segments are transformed into
more anterior abdominal segments in
abd-A and abd-B mutant embryos
Homeotic mutation that converts antennae into legs
- ANTP mis-expression
* ANTP in T segment represses genes anterior to it (antennae and eyes) and switch on downstream
How do homeotic genes determine the identity of individual segments?
homeotic genes activate or repress Realisator Genes
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Antennapedia inhibits
• antenna forming genes
• eye forming gene
eyeless/Pax6
and posterior
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Ultrabithorax represses
wing development
The order of Hox genes is similar between
insects and mammals
• we have overlapping patterns and more Hox genes
Hox 10 knockout
transformation of lumbar into thoracic vertebrae
Expansion of Hox 10 –>
Hox 11 knockout
Hox 11 knockout
transformation of sacral into lumbar vertebrae
A code of differing Hox gene expression determines
the type of vertebrae formed
segmented structures of mesoderm
In vertebrates, there are hox genes
for limbs (prox/dist) as well as anterior-posterior axis
Hox genes prepattern the
limb bud along the anterior-posterior axis
There may be 1 enhancer for
many genes
And many enhancers for 1 gene
Mutations in Hox 11, 12, and 13 in early limb buds lead to a loss of
ASYMMETRY
Hox gene expression changes
during the development of the limbs
Shh is a
transcription factor
The late expression of Hox genes is required for
patterning of the proximal-distal limb axis
overlapping –> structures form on prox/dist axis
Radius and ulna are missing in
Hox-11 deficient mouse mutants
Mutations in Hox 13 humans lead to
polysyndactyly - “many fingers joint together”
ant/post axis
Homeodomain proteins determine
regional identity along the dorso-ventral axis
patterning of the nervous system
Homeodomain proteins … … and … subdivide the neuroectoderm into 3 dorso-ventral regions
- Msh
- Ind
- Vnd
specific neurons formed in different areas
The dorso-ventral homeodomain proteins are conserved in
vertebrates although the nerve cord is dorsal
Homeodomain proteins determine the
identity of body segments along the anterior-posterior axis
Homoetic selector genes are arranged on the chromosome(s)
in the same sequence as they are expressed along the anterior-posterior axis
Mutations in homeotic selector genes result in
transformations
Vertebrate Hox genes determine the identity of the
vertebrae along the anterior-posterior axis
Vertebrate hox genes are required for
patterning the anterior-posterior and proximal-distal axis in the developing limb
Homoedomain proteins establish regional identity in the
neuroectoderm along the dorso-ventral axis, both in vertebrates and invertebrates
Antennapedia inhibits
• antenna forming genes
• eye forming gene
(eyeless/Pax6)
and posterior
