Model Organisms in Development Biology

Model Organisms for Studying Development

• Traditional embryology focused on egg-laying animals.
• Development is external to the mother's body (ex utero).
• Eggs are large and embryos are easily manipulated (e.g., transplants, grafts).
• Examples include Xenopus laevis and the chicken.
• Contemporary research focuses on developmental genes.
• Requires animals with large populations and short generation times for genetic analysis.
• The fruit fly Drosophila melanogaster provides the most insight.

Nobel Prize in Physiology or Medicine 1995

• Awarded jointly to Edward B. Lewis, Christiane Nüsslein-Volhard, and Eric F. Wieschaus.
• Recognizing their discoveries concerning the genetic control of early embryonic development.

Drosophila Development: The Body Plan

• Drosophila genes controlling development are similar to those in vertebrates.
• Drosophila is the best understood developmental system, providing crucial knowledge about development in general.
• Hox genes were first found in Drosophila.
• Bilateral symmetry is established by the anterior-posterior (A/P) and dorsal-ventral (D/V) axes.
• Early patterning occurs in the syncytial blastoderm and eventually becomes multicellular at the start of segmentation.
• Concentration gradients of proteins (transcription factors) diffuse and enter nuclei, providing positional information.

Drosophila Development: Maternal Genes

• Maternal genes establish the body axes.
• Maternal gene products (mRNAs and proteins) are expressed in the ovary.
• Zygotic genes are expressed by the embryo.
• About fifty maternal genes establish anterior-posterior (A/P) and dorsal-ventral (D/V) axes, providing spatial information (distributing RNAs and proteins).
• Zygotic genes respond to maternal gene expression.
• Broad regions are initially established, followed by smaller domains with unique zygotic gene activities arranged in a hierarchy of gene activity.

Drosophila Development: The A/P Axis

• Three classes of maternal genes set up the anterior-posterior (A/P) axis.
• Maternal genes distinguish anterior from posterior regions.
• Maternal effect mutants create females that produce abnormal offspring.
• Mutant classes include anterior, posterior, and terminal classes with effects on head, thorax, abdominal segments, acron, and telson.
• Key maternal genes involved in A/P axis formation include bicoid, hunchback, oskar, nanos, and caudal.

Drosophila Development: Maternal Genes (Oocyte)

• Bicoid mRNA is sequestered in the oocyte during oogenesis and localized to the anterior end of the unfertilized egg.
• After fertilization, bicoid mRNA is translated, forming a concentration gradient along the A/P axis.
• Bicoid establishes an A/P morphogenic gradient and controls early steps in embryo development. It's crucial for the developing organism.

Drosophila Development: Clues to the Role of Bicoid

• Bicoid (bcd) mutant females lay eggs producing embryos lacking heads and thoraxes.
• Embryos missing anterior cytoplasm display similar developmental defects.
• Anterior cytoplasm in bcd embryos can induce ectopic head and thoracic segments. In-situ hybridization shows bcd mRNA in the anterior region of the unfertilized egg, attached to the cytoskeleton.
• After fertilization, bcd mRNA is translated into a protein, establishing an A/P gradient.
• Bicoid is a transcription factor and morphogen.
• Other anterior-group maternal genes are involved in bicoid localization and translational control.

Methods to Determine mRNA and Protein Localization

• mRNA: in situ hybridization uses DNA complementary to specific mRNA, combined with an alkaline phosphatase-conjugated antibody. This allows identification of mRNA locations.
• Protein: antibody staining permeabilizes cells, allows incubation with specific antibody conjugates, and visualizes antibody binding.

Maternal Nanos Blocks Translation of Maternal Hunchback mRNA

• Maternal nanos blocks the translation of hunchback mRNA.
• This results in different protein concentrations.

A/P Axis is Divided into Broad Regions by Gap Genes

• Gap genes, the first genes expressed along the A/P axis, are transcription factors (TFs).
• Gap gene expression is controlled by bicoid.
• Hunchback helps switch on other gap genes: giant, Krüppel, and knirps.
• Gap gene mutations result in missing body sections.
• Gap gene proteins are short-lived and have bell-shaped concentration distributions.

Krüppel Gene Expression

• Krüppel is activated by bicoid and low levels of hunchback, but repressed by high hunchback levels.
• This positions Krüppel expression at the center of the embryo.
• Knirps is repressed by high hunchback levels.
• These gradients of morphogens lead to syncytial blastoderm organization and the beginning of segmentation.

Expression of Zygotic Hunchback

• Hunchback expression is localized to the anterior half of the embryo.
• Suppression in the posterior half creates an A-to-P gradient.
• Bicoid (a homeodomain transcription factor) directly binds the hunchback promoter, activating its expression.

Investigating Interactions Between Transcription Factors and Promoters

• Fuse a promoter region to a reporter gene (like lacZ or GFP).
• Create a transgenic animal with the fusion construct.
• Monitor reporter gene product expression (e.g., using histological stains or fluorescent microscopy).

Explore the role of model organisms like Drosophila and Xenopus in understanding developmental biology. This quiz covers their developmental mechanisms, genetic insights, and contributions to the Nobel Prize in Physiology or Medicine 1995. Test your knowledge on how these organisms have shaped our understanding of embryonic development.