Drosophila Body Plan and Segmentation Genes

Drosophila Body Plan

  • Drosophila body plan is established through the sequential action of three types of segmental genes:
    • Maternal effect genes (e.g., bicaudal).
    • Segmentation genes.
    • Segment-polarity genes.

Maternal Effect Genes

  • These genes are expressed by the mother and their products are deposited in the oocyte, establishing the initial anterior-posterior axis.
  • Examples include:
    • bicoid (bcd):
      • Maternal (M) gene.
      • Encodes a homeodomain transcription factor (T).
      • Functions as a morphogen, providing positional information along the anterior-posterior (AP) axis; represses caudal mRNA.
      • Mutant phenotype: Head and thorax deleted, replaced by inverted telson
    • hunchback (hb):
      • Maternal and zygotic (M/Z) gene.
      • Encodes a zinc finger transcription factor (T).
      • Functions as a morphogen providing positional information along the AP axis.
    • nanos (nos):
      • Maternal (M) gene.
      • Encodes an RNA-binding protein.
      • Helps to establish the AP gradient of hunchback protein; Posterior morphogen; represses hunchback mRNA.
      • Mutant phenotype: No abdomen
    • caudal (cad):
      • Maternal (M) gene.
      • Encodes a homeodomain transcription factor (T).
      • Involved in specifying the posterior region; Activates posterior terminal genes.
      • Mutant phenotype: No abdomen
    • gurken:
      • Maternal (M) gene.
      • Encodes a secreted protein of the TGF-α family (S).
      • Involved in posterior oocyte-follicle cell signaling and specifies the oocyte axis.
      • Anchors bicoid mRNA
    • oskar (osk):
      • Maternal (M) gene.
      • Involved in pole-cell determination; Localization of Nanos protein.
      • Mutant phenotype: No abdomen, no pole cells

Terminal System Genes

  • These genes are involved in specifying the terminal regions of the embryo.
    • Example:
      • torso (tor):
        • Maternal (M) gene.
        • Encodes a receptor tyrosine kinase (R).
        • Involved in terminal specification.
        • Mutant phenotype: No termini
      • trunk (trk):
        • Maternal (M) gene.
        • Encodes a signal protein (S).
        • Ligand for torso; Transmits Torso-like signal to Torso.
        • Mutant phenotype: No termini

Gap Genes

  • These zygotic (Z) genes are expressed in broad domains along the AP axis, dividing the embryo into regions.
  • Examples include:
    • hunchback (hb):
      • Zygotic (Z) gene.
      • Encodes a zinc finger transcription factor (T).
      • Localizes pair-rule gene expression.
    • Krüppel (Kr):
      • Zygotic (Z) gene.
      • Encodes a zinc finger transcription factor (T).
      • Localizes pair-rule gene expression.
    • knirps (kni):
      • Zygotic (Z) gene.
      • Encodes a zinc finger transcription factor (T).
      • Localizes pair-rule gene expression.
    • giant (gt):
      • Zygotic (Z) gene.
      • Encodes a leucine zipper transcription factor (T).
      • Localizes pair-rule gene expression.
    • tailless (tll):
      • Zygotic (Z) gene.
      • Encodes a zinc finger transcription factor (T).
      • No termini.

Pair-Rule Genes

  • These zygotic (Z) genes are expressed in alternating stripes, dividing the embryo into parasegments.
  • Examples include:
    • even-skipped (eve):
      • Zygotic (Z) gene.
      • Encodes a homeodomain transcription factor (T).
      • Delimits odd-numbered parasegments.
    • fushi tarazu (ftz):
      • Zygotic (Z) gene.
      • Encodes a homeodomain transcription factor (T).
      • Delimits even-numbered parasegments.
    • hairy (h):
      • Zygotic (Z) gene.
      • Encodes a helix-loop-helix transcription factor (T).
      • Involved in segmentation.
    • runt (run):
      • Zygotic (Z) gene.
      • Involved in segmentation.

Segment Polarity Genes

  • These zygotic (Z) genes are expressed in each segment, defining the anterior and posterior compartments.
  • Examples include:
    • engrailed (en):
      • Zygotic (Z) gene.
      • Encodes a homeodomain transcription factor (T).
      • Defines the anterior region of a parasegment and the posterior region of a segment.
    • hedgehog (hh):
      • Zygotic (Z) gene.
      • Encodes a membrane or secreted signal protein (S).
      • Component of signaling pathways that pattern segments and stabilize compartment boundaries.
    • wingless (wg):
      • Zygotic (Z) gene.
      • Encodes a secreted signal protein (S).
      • Component of signaling pathways that pattern segments and stabilize compartment boundaries.
    • frizzled (fz):
      • Zygotic (Z) gene.
      • Encodes a membrane receptor protein (R).
      • Component of signaling pathways that pattern segments and stabilize compartment boundaries.
    • gooseberry (gsb):
      • Zygotic (Z) gene.
      • Encodes a homeodomain transcription factor (T).
    • patched (ptc):
      • Zygotic (Z) gene.
      • Encodes a membrane receptor protein (R).
      • Component of signaling pathways that pattern segments and stabilize compartment boundaries.
    • smoothened (smo):
      • Zygotic (Z) gene.
      • Encodes a G-protein-coupled receptor (R).
      • Component of signaling pathways that pattern segments and stabilize compartment boundaries.

Selector Genes

  • These genes determine the identity of each segment.
  • Examples include:
    • bithorax complex:
      • Ultrabithorax (Ubx):
        • Zygotic (Z) gene.
        • Encodes a homeodomain transcription factor (T).
        • Combinatorial activity confers identity on parasegments 5-13.
      • abdominal-A (abd-A):
        • Zygotic (Z) gene.
        • Encodes a homeodomain transcription factor (T).
        • Combinatorial activity confers identity on parasegments 5-13.
      • Abdominal-B (Abd-B):
        • Zygotic (Z) gene.
        • Encodes a homeodomain transcription factor (T).
        • Combinatorial activity confers identity on parasegments 5-13.
    • Antennapedia complex:
      • Deformed (Dfd):
        • Zygotic (Z) gene.
        • Encodes a homeodomain transcription factor (T).
        • Combinatorial activity confers identity on parasegments anterior to 5.
      • Sex combs reduced (Scr):
        • Zygotic (Z) gene.
        • Encodes a homeodomain transcription factor (T).
        • Combinatorial activity confers identity on parasegments anterior to 5.
      • Antennapedia (Antp):
        • Zygotic (Z) gene.
        • Encodes a homeodomain transcription factor (T).
        • Combinatorial activity confers identity on parasegments anterior to 5.
      • labial (lab):
        • Zygotic (Z) gene.
        • Encodes a homeodomain transcription factor (T).
        • Combinatorial activity confers identity on parasegments anterior to 5.

Maintenance Genes

  • These genes maintain the expression state of the homeotic genes.
  • Examples include:
    • Polycomb group (PcG):
      • Zygotic (Z) genes.
      • Maintain the repressed state of homeotic genes.
    • Trithorax group (TrxG):
      • Zygotic (Z) genes.
      • Maintain the active state of homeotic genes.

Dorso-Ventral System

  • Maternal genes establish the dorso-ventral axis.
    • Toll: Membrane receptor (R).
    • spätzle: Extracellular ligand for Toll protein (S).
    • dorsal: Transcription factor (T); Activation results in Dorsal protein entering the nucleus.
    • tube: Adaptor protein.
    • pelle: Protein kinase.
    • cactus: Cytoplasmic inhibitor; degraded, releasing it from Dorsal.
    • gurken: Secreted protein (S); Specifies oocyte axis
    • pipe: Sulfotransferase; Part of pathway leading to Spätzle processing
  • Zygotic genes refine the dorso-ventral axis.
    • twist: Helix-loop-helix transcription factor (T); Defines mesoderm.
    • snail: Zinc finger transcription factor (T); Defines mesoderm.
    • rhomboid: Membrane protein (S).
    • zerknüllt: Homeodomain transcription factor (T); Amnioserosa
    • decapentaplegic: Secreted protein of the TGF-β family (S); Dorsal ectoderm
    • tolloid: BMP-2 family (S).
    • short gastrulation: Confer regional identity on the dorso-ventral axis (S).

Sequential Expression of Segmentation Genes

  • Models suggest a sequential expression pattern: maternal genes $\rightarrow$ gap genes $\rightarrow$ pair-rule genes $\rightarrow$ segment polarity genes.

Process of Anterior-Posterior Axis Specification

  • The anterior-posterior axis is defined by:
    • Oocyte cytoplasm.
    • Embryonic regions.
    • Groups of two segments.
    • Single segments.
    • Compartments within segments.

Syncytial Specification

  • In Drosophila, specification occurs in a syncytium (a multinucleate cell).
  • Gradients of Bicoid (anterior) and Nanos (posterior) proteins are established.
    • Bicoid mRNA is concentrated at the anterior.
    • Nanos mRNA is located in the posterior.
  • These gradients lead to the formation of:
    • Acron (head cap).
    • Head-forming region.
    • Thorax-forming region.
    • Abdomen-forming region.
    • Telson (tail).

Bicoid and Caudal Protein Gradients

  • Bicoid protein forms a gradient with the highest concentration at the anterior end.
  • Caudal protein gradient is also established in the syncytial blastoderm.
  • This involves mRNA localization and translational regulation.

Torso Signaling

  • Torso signaling is responsible for forming unsegmented extremities.
  • Involves the activation of Torso receptor by Torso-like signal.
  • This leads to the activation of downstream targets like huckebein (hkb) and tailless (tll).

Mutations in Segmentation Genes

  • Gap gene mutations (e.g., Krüppel) result in the deletion of a contiguous group of segments.
  • Pair-rule gene mutations (e.g., fushi tarazu) cause the deletion of alternating segments.
  • Segment polarity gene mutations (e.g., engrailed) affect the pattern within each segment.

Overlap and Integration of Segments and Parasegments

  • Segments and parasegments are overlapping units.
  • Parasegments are the fundamental units of gene expression.

Regulatory Interactions Among Gap Genes

  • Gap genes regulate each other's expression.
  • Examples include Krüppel (Kr), knirps (kni), hunchback (hb), and giant (gt).
  • These interactions refine the expression domains of gap genes.

Even-Skipped (eve) Gene Regulation

  • Specific promoter regions of the even-skipped (eve) gene control specific transcription bands in the embryo.
  • Different enhancers drive expression in different stripes.

Engrailed and Wingless Transcription

  • Model for transcription of the segment polarity genes engrailed (en) and wingless (wg).
  • Initiation by products of pair-rule genes.
  • Interaction between engrailed and wingless.
  • Diffusion of Wingless and Hedgehog proteins.

Homeotic Selector Genes and Homeobox

  • Mutations in homeotic selector genes result in the transformation of one body part into another.
  • Each homeotic gene has a 180 base pair DNA sequence in common, called the homeobox.
  • The peptide counterpart is the homeodomain.
  • Some maternal effect and segmentation genes also contain homeoboxes.

Homeotic Gene Expression

  • Homeotic genes are expressed in specific domains along the AP axis.
  • Examples include Antennapedia (Antp), Ultrabithorax (Ubx), and Abdominal-B (AbdB).

Role of Ultrabithorax

  • Lewis proposed that T2 is the ground state.
  • Subsequent segments have additional genes active (e.g., T3 has T2+ T3 genes active).
  • First abdominal segment (A1) would have T2, T3, and A1 genes active.

Cartesian Coordinate System

  • Gene expression patterns map out a Cartesian coordinate system.
  • Examples include:
    • short gastrulation (red).
    • int. neuroblast defect (green).
    • musclesegment homeobox (magenta).
    • wingless (yellow).
    • engrailed (blue).
    • Scr (sex combs reduced).
    • Dpp (decapentaplegic).

Maternal Effect Genes Table

  • Anterior Group:
    • Mutant phenotype: Head and thorax deleted, replaced by inverted telson
    • Genes: bicoid, exuperantia, swallow
  • Posterior Group:
    • Mutant phenotype: No abdomen
    • Genes: nanos, tudor, oskar, vasa, valois, pumilio, caudal
  • Terminal Group:
    • Mutant phenotype: No termini
    • Gene: torso, trunk, fs(1)Nasrat, fs(1)polehole

Major Genes Affecting Segmentation Pattern in Drosophila

  • Gap genes: Krüppel, knirps, hunchback, giant, tailless, huckebein, buttonhead, empty spiracles, orthodenticle
  • Pair-rule genes (primary): hairy, even-skipped, runt
  • Pair-rule genes (secondary): fushi tarazu, odd-paired, odd-skipped, sloppy-paired, paired
  • Segment polarity genes: engrailed, wingless, cubitus interruptusD, hedgehog, fused, armadillo, patched, gooseberry, pangolin