Genetic control of complex phenotypes:
      Developmental Genetics of Drosophila


In Principle:
    All cells contain the same DNA genome
           Genome: the complete set of genes in a cell - constant
    Differences among cells reflect differences in genome expression
        timing, amount, & location of RNA transcription & protein translation
           Proteome: the complete set of proteins in a particular cell,
                               in a particular tissue, or at a given developmental stage
            The proteome is therefore highly variable

     Developmental cascades of genes that activate other genes
(MGA2 16 Chapter Overview)
          Basic patterns are the result of relatively few genes
          Variable patterns arise from simple 'switches'


Overview of insect development:
    insects are tripartite
(MGA2 16-26a)
        Early development forms monolayer blastoderm (MGA2 16-14, 22)
        Subsequent "fate" of cells predictable from position in fate map
        3 Head + 3 Thorax + 9 Abdomen segments (MGA2 16-23)
              anterior & posterior compartments in each
        Cuticular structures develop from imaginal disks
              12 disks are associated with segments
              e.g., wings from T2, halteres from T3

 Genetics of early embryogenesis
 The genetic approach: (C. Nüsslein-Volhard and E. Wieschaus: Nobel Prize in 1995)
      Infer nature of wild-type by observation of mutant phenotype
      Induce recessive alleles with embryonic-lethal effects:
           Mm x Mm  1 / 4 mm & fail to develop (lethal) or
           Mm [f] x Mm [p] 
all embryos are 'M' : maternal effect (MGA2 Foundations 3)
           e.g.: at bicoid locus: bcd / bcd has no head or thorax structures (MGA2 16 Foundations 4)
                
gene affects anterior / posterior (A / P) axis formation
                increasing dose of bcd+ increases "cephalization" (MGA2 Foundations 4)
                     displaces "head" to more posterior position
   Conclusion: Drosophila development is determined by a limited number of gene sets
        Activated as ordered cascades (MGA2 16-28)

   Maternal-Effect genes (Table 16.3)
           Gene products (mRNA & protein) are present in egg (maternal) cytoplasm
           anterior / posterior (A / P) gradients form in egg
                (mRNAs are anchored to microtubules in cytoskeleton) (MGA2 16-21a)

   bicoid locus affects formation of anterior head & thoracic structures
        bcd+ mRNA localized at anterior pole of egg  (MGA2 16-16 a,b)
        BCD protein forms A / P gradient
   nanos locus affects formation of posterior abdominal segments
        nos+ mRNA expressed at posterior pole of egg (MGA2 16 c,d)
        NOS protein inhibits translation of hunchback (hb-m) locus
             expression  of HB-M protein in zygote is
                  enhanced by bicoid,
                  inhibited by nanos
                   => Gradient of HB-M concentration exists in zygote
       Cells "read" positional information as to their place on A / P axis (MGA21 16-21b)
             cells can be "fooled" to misread the information (MGA2 16-17)

   Zygotic genes  (Overview of phenotypes) (MGA2 16-24)
        Transcription of biparental genes is induced by maternal-effect genes ("French Flag" model)

        Gap genes
                determination of tri-partite body pattern:
                       roughly, head, thorax, & abdomen (MGA2 16-25a) (MGA2 16 Foundations 4)

        Pair-Rule genes
                determination of segments
                segment patterns are repetitive (iterative) (MGA2 16-25b)
                Segment patterns are determined by multiple, independent "rules"

        Segment Polarity genes
                determination of anterior & posterior compartments within segments

   Homeotic selector genes
            Determine phenotypic expression of segment
            Control differentiation of imaginal discs
        
Transdetermination
            Homeotic mutants alter fate of imaginal discs (E. B. Lewis 1945: Nobel Prize 1995)
              Bithorax transforms halteres (T3)  wings (T2)
                    Note that flies are "Diptera", but bithorax has four wings (MGA2 16-26c)
                    alternative expression of Ubx gene complex
              antennapedia (nasobemia) transforms antennae legs
                    alternative expression of Antp gene complex


All text material © 2008 by Steven M. Carr