homeotic genes in drosophila body patterning
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Homeotic genes in Drosophila body patterning. Genetics Unit, Department of Biochemistry [email protected]. Developmental biology: Drosophila segmentation and repeated units. * egg: generate the system. * larva: eat and grow. * pupa: structures in - PowerPoint PPT PresentationTRANSCRIPT
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Developmental biology: Drosophila segmentation and repeated units
1
* egg: generate the system
* larva: eat and grow
* pupa: structures inlarvae grow out to form adult fly: metamorphosis
(Drosophila is a holometabolous insect)
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Homeotic gene complexes in Drosophila
• ANT-C (Antennapedia complex) is largely responsible for segmental identity in the head and anterior thorax.
• BX-C (Bithorax complex) is responsible for segmental identity in the posterior thorax and abdomen.
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HOMEOSIS
• Homeosis or homeotic transformation, is the development of one body part with the phenotype of another.
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The bithorax mutations
• This class of loss of functions mutations cause the entire third thoracic segment to be transformed into a second thoracic segment giving rise to flies with four wings instead for the normal two.
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The Tab dominant mutations
• These gain of function mutations transform part of the second thoracic segment into the sixth abdominal segment.
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The Antennapedia mutations
• These gain of function mutations transform antenna into leg.
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The Homeodomain
• The homeotic genes encode transcription factors of a class called homeodomain proteins. The homeodomain is a 60aa protein domain, which binds DNA. Hox genes bind DNA regulatory elements of their target genes in a specific combination so that the expression pattern in each of the different segments is unique.
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The mystery of the homeodomain specificity
• In vitro, homeodomains have a very broad binding specificity, which does not explain the refined specific regulation of target genes observed in vivo. So how can this be explained?
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The co-linearity principle: Homeotic gene expression in Drosophila
• The anterior boundary of homeotic gene expression is ordered from SCR (most anterior to ANTP, UBX and ABD-B (most posterior). This order is matched by the linear arrangement of the corresponding genes along chromosome 3.
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Mechanisms underlying functional diversity of Hox
proteins
Understanding how function is encoded within Hox protein structure
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The co-factor hypothesis
• There is the possibility of specific co-factors, which are expressed in the domain of expression of the Hox-gene. Until now very few were found, the most prominent example being Extradenticle and Homothorax (EXD, HTH; Ryoo et al, Development 126, pp 5137-48, 1999).
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A2
A1
T2
T3
T1 Gebelein et al, Dev. Cell, 2002
Dll repression: a paradigm for the study of Hox/Exd interaction
DME-lacZ / Ubx
UbxAbdA DllExd +
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The DNA sequence motif hypothesis
• Different combination of DNA modules would give different combination of co-factors bound on the promoter and thus a different array of transcriptional interactions with each Hox protein (Li et al, Development 126, 5581-5589, 1999).
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Insect vs. mammalian Hox genes
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Expression patterns of mouse Hox genes
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Phenotype of a homeotic mutant mouse
• Mice mutant for a targeted knockout of the HoxC8 gene reveal ribs duplication and a clenched-fingers phenotype.
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Developmental strategies in animals are ancient and highly conserved. In essence, a mammal, a worm and a fly-three very different organisms-are put together with the same basic building blocks and regulatory devices.
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Is there a “ground” state?
Changes in Hox gene expression can help explain the evolution of
arthropod body plans
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Wild type
Hox mutant
Lewis et al. 2000
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Averof and Patel 1997
Averof and Patel 1997 Nature 388, 682-686Averof 2002 Curr Op Genetics and Development 1386-392
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Insects
Branchiopoda (Artemia, the brine-shrimp)
Malacostracans (Lobsters, hermit crabs)
Expression of Hox genes in arthropods
crustaceans
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species 1 species 2
Evolution of crustacean maxillipeds
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Triops (no mxp): Ubx expression in all thoracic segments
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T1
T2
T3
T1
T2
T3
Mysid (1 mxp): Ubx expression from T2 to the posterior
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Reading ListTextbooks: 1). Scott F Gilbert (2003). Developmental Biology 7th edition, chapter 9, pp285-290; 2). Wolpert Evolution and development chapter in Principles of developmentGeneral review: McGinnis W and Krumlauf R (1992). Homeobox genes and axial patterning Cell, 68, pp283-302.Evolution of body pattern review: Averof M (2002) Curr Op Genetics and Development 1386-392