Drosophila Development and Hierarchical Control

Hierarchical Control in Development

• One of the fundamental principles of complex multicellular organism development is the hierarchical control of gene expression.

  • Genes expressed early in development activate or repress other gene groups that function later.

  • This creates a cascade where genes at each stage control the expression of genes in subsequent stages.

Drosophila melanogaster as a Model System

• The fruit fly Drosophila melanogaster is a crucial model for understanding genetic control of early development, especially hierarchical control.

• Researchers have identified and analyzed numerous mutant genes causing developmental defects, revealing key genes and processes.

Drosophila Life Cycle and Early Embryonic Development

• The Drosophila life cycle includes egg, larval, pupa, and adult stages (Fig. 18.5).

• Fertilization and Early Nuclear Divisions:

  • DNA replication and nuclear division commence rapidly after egg and sperm nuclei fuse (Fig. 18.5a).

  • Unlike mammalian development, early nuclear divisions occur without cell division.

  • The embryo initially exists as a single, multinucleated cell with approximately 5000 nuclei concentrated in the center (Fig. 18.5b).

• Cellular Blastoderm Formation:

  • Nuclei migrate to the cell's periphery (Fig. 18.5c).

  • Each nucleus becomes enclosed within its own cell membrane, forming the cellular blastoderm (Fig. 18.5d).

• Gastrulation:

  • Cells of the blastoderm migrate inward.

  • This process creates the three primary germ layers: ectoderm, mesoderm, and endoderm (similar to humans and other animals, Section 18.1 and Chapter 41).

  • These germ layers subsequently differentiate into various cell types.

  • A Drosophila embryo during gastrulation is depicted in Fig. 18.5e.

• Segmentation:

  • Even at the gastrulation stage, the embryo exhibits distinct segments.

  • These include: three cephalic (head) segments (C1-C3), three thoracic (middle region) segments (T1-T3), and eight abdominal segments (A1-A8).

  • Each segment has a unique developmental fate.

• Larval Stage:

  • Approximately one day post-fertilization, the embryo hatches as a larva (Fig. 18.5f).

  • For the next eight days, the larva grows and molts (replaces its cuticle) twice (Figs. 18.5g and 18.5h).

• Pupal Stage and Metamorphosis:

  • After further growth, the cuticle forms a protective casing called the pupa (Fig. 18.5i).

  • Within the pupa, the larva undergoes dramatic developmental changes known as metamorphosis, leading to the adult fruit fly (Fig. 18.5j).

Maternal Effect Genes and Early Patterning

• Pioneering Research: Christiane Nüsslein-Volhard and Eric F. Wieschaus were awarded the 1995 Nobel Prize in Physiology or Medicine for their systematic studies of Drosophila mutants, which elucidated how genes control development.

• Oocyte Maturation: Development begins even before fertilization, during the maturation of the mother's unfertilized egg cell (oocyte).

  • The oocyte's maturation, controlled by maternal genes, is critical for normal embryonic development.

  • This principle applies to Drosophila and many other multicellular animals.

• Mutant Phenotypes: Nüsslein-Volhard and Wieschaus investigated mutants affecting early development, visible by the larval stage (Fig. 18.6).

  • Bicoid Mutants: Larvae are missing segments at the anterior (head) end (Fig. 18.6b).

  • Nanos Mutants: Larvae are missing segments at the posterior (tail) end (Fig. 18.6c).

  • These mutant larvae are severely abnormal and non-viable.

  • The missing segments were identified by their distinctive hairlike projections (dark shapes in Fig. 18.6).

• Maternal Effect Genes Defined:

  • A key feature of bicoid and nanos mutants is that the embryonic abnormalities depend on the mother's genotype, not the embryo's genotype.

  • This is because successful development requires the mother to produce a functional oocyte.

  • The egg's composition includes macromolecules (e.g., RNA, protein) synthesized by maternal cells and transported into the egg.

  • Mutations in maternal genes affecting oocyte development lead to abnormalities in the offspring.

  • Genes like bicoid and nanos, expressed by the mother but influencing offspring phenotype, are called maternal effect genes.

• Establishing Anterior-Posterior Polarity:

  • A normal Drosophila oocyte is highly polarized, meaning its ends are distinct.

  • Gradients of macromolecules establish the anterior-posterior (head-to-tail) and dorsal-ventral (back-to-belly) axes.

  • The most well-known gradients involve messenger RNAs (mRNAs) from the maternal effect genes bicoid and nanos (Fig. 18.7).

• Bicoid Gradient:

  • bicoid mRNA from the mother is localized primarily at the anterior end of the egg, anchored by proteins to the cytoskeleton (Fig. 18.7a).

  • After fertilization, Bicoid protein is produced from this mRNA, forming an anterior-to-posterior concentration gradient.

• Nanos Gradient:

  • nanos mRNA, also synthesized by maternal cells and imported during oogenesis, is largely concentrated at the posterior end of the egg (Fig. 18.7b).

  • Following fertilization, Nanos protein is translated, creating a posterior-to-anterior concentration gradient.

• Reinforcement by Caudal and Hunchback:

  • The anterior-posterior axis, initiated by Bicoid and Nanos, is reinforced by gradients of two transcription factors: Caudal and Hunchback (Fig. 18.8).

  • Their mRNAs are also transcribed from the mother's genome and transported uniformly into the egg cytoplasm (Fig. 18.8a).

  • However, their translation is not uniform in the fertilized egg.

  • Bicoid protein represses the translation of caudal mRNA, leading to high Caudal protein concentration at the posterior end.

  • Nanos protein represses the translation of hunchback mRNA, resulting in high Hunchback protein concentration at the anterior end (Fig. 18.8b).

  • This demonstrates gene regulation at the translational level (Chapter 17).

• Role of Hunchback and Caudal Gradients:

  • The Hunchback and Caudal gradients establish the foundation for subsequent developmental steps.

  • Hunchback (anteriorly concentrated) targets embryonic genes crucial for anterior structures (e.g., eyes, antennae).

  • Caudal (posteriorly concentrated) targets embryonic genes essential for posterior structures (e.g., genitalia).

  • Thus, maternal genes significantly influence the expression of embryonic genes later in development.

  • Consequently, bicoid mutant mothers lack larvae with anterior structures, and nanos mutant mothers lack larvae with posterior structures, due to the products of these mRNAs organizing the embryo's ends.

Embryonic Developmental Genes: Progressive Regionalization and Specification

• Nüsslein-Volhard and Wieschaus also discovered mutations in genes expressed by the embryo itself.

• These genes are activated in groups, with each successive group spatially restricting and refining the differentiation pattern established by earlier groups, a general principle in many multicellular organisms.

• Three classes of embryonic developmental genes were identified:

1. Gap Genes

• Function: Refine the anterior-posterior gradient set up by maternal effect genes.

• Expression Pattern: Each gap gene is expressed in a broad region of the embryo.

• Mutant Phenotype: Mutant embryos are missing contiguous groups of segments, creating a