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Drosophila homeotic mutants. Homeotic (Hox) gene complexes in Drosophila. lab. pb. Dfd. Scr. Antp. Ubx. abdA. AbdB. labial. Deformed. Antennapedia. abdominal-A. proboscipedia. Sex combs reduced. Ultrabithorax. Abdominal-B. Antennapedia Complex (ANT-C). Bithorax Complex (BX-C).
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Homeotic (Hox) gene complexes in Drosophila lab pb Dfd Scr Antp Ubx abdA AbdB labial Deformed Antennapedia abdominal-A proboscipedia Sex combs reduced Ultrabithorax Abdominal-B Antennapedia Complex (ANT-C) Bithorax Complex (BX-C)
labial Antennapedia Ultrabithorax proboscipedia Deformed abdominal A Sex combs reduced Abdominal B Expression patterns of homeotic genes in embryogenesis pb Ubx AbdB Dfd Scr Antp abdA lab
Two types of homeotic mutants in Drosophila dominant mutations gain-of-function Transformations “anterior to posterior“ recessive mutations loss-of-function Transformations “posterior to anterior“
Antennapedia - a homeotic mutant antennenal segments Arista coxa claw troch- anter tarsal segments tibia femur Antp / + antenna and leg are serially homologous limbs antenna transformed into leg
proboscipedia - transformation of mouthparts into legs mx mx* lb lb*
Bithorax Complex (BX-C) regulatory mutations Coding-region mutations Complex homeotic gene regulation
Ultrabithorax binds DNA and regulates genes required for T3 and A1 T3,A1 Ultrabithorax expression Ubx protein OFF ON T2 specific gene OFF T3 specific gene ON A5 specific gene A1 specific gene
All abdominal segments take on a T2 identity if the bithorax complex is deleted ubxabdA abdB triple mutant Wild type T2 T3 A1 T2 T2 T2 A8 T2
Antennapedia expression expands in flies mutant for the Bithorax complex genes ANT-C BX-C
Ultrabithorax, AbdA, and AbdB normally repress expression of the thorax-specific “leg gene” Distalless in the abdominal segments wild-type ubxabdA abdB triple mutant abdomen T1 T2 T3
Persistence of homeotic gene expression through development Adult Imaginal discs larva embryo
Maintenance of homeotic gene expression trithorax group (Trx-G) maintenance of transcriptionally activestate maintenance of transcriptionally inactive state Polycomb group (Pc-G) Trx-G Pc-G transcriptionally open chromatin transcriptionally closed chromatin pb Dfd Scr Antp extradenticle Exd Dfd realisator gene
Lewis hypothesized that the duplication and diversification of homeotic master regulators underlies the evolution of an increasingly complex body plan
Distal-less gene required for limb development Drosophila Precis (butterfly)
The human body is also built up from reiterated units (segments) with different identities along the A/P axis
Mouse hoxa3 and hoxd3 mutants from Nature 370: 304-307 (1994)
Wild-type mouse forelimb hoxa-11 hoxd-11 Human hoxD13 mutation