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Developmental Genetics

Developmental Genetics. How Selective Gene Expression Determines the Developmental Fate of Specific Cells -Chapter 16, pages 460-462 -Chapter 21, pages 604-612. Definitions. Determination = process of commitment of a cell to a particular fate

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Developmental Genetics

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  1. Developmental Genetics How Selective Gene Expression Determines the Developmental Fate of Specific Cells -Chapter 16, pages 460-462 -Chapter 21, pages 604-612

  2. Definitions • Determination = process of commitment of a cell to a particular fate • Differentiation = changes in cell shape and physiology associated with production of final cell type • Developmental field = a set of cells that together interact to form a developing structure • Morphogen = substance that specifies cell identity as a function of its concentration

  3. Gene Expression • Differentiation depends upon the expression of a specific subset of genes. • Gene expression can be controlled at any level between transcription and activation of the protein product.

  4. Transcriptional Control Post-Transcriptional Control Translational Control Post-Translational Control Control Points for Gene Expression in Eukaryotes DNA transcription RNA processing translation Protein

  5. Developmental “Decisions” • Binary decisions Separation of germ line from soma Establishment of gender* • Choosing one fate from multiple options Axis formation* Segmentation* Germ layer formation Organogenesis

  6. Balance of Active Transcription Factors Presence or Absence Of Sxl Protein Sxl Protein Regulates Splicing of its own mRNA Fru ProteinsControl Sex-Specific Behavior Sxl Protein Regulates Splicing of tra mRNA Tra Proteins RegulateSplicing of fru mRNA Dsx Proteins Activate or Repress Transcription of Sex-Specific Genes Tra Protein Regulates Splicing of Dsx mRNA Ratio of Sex Chromosomesto Autosomes (X:A) A Cascade of Events Affects Expression of Sex-specific Traits in Drosophila

  7. Effects of X:Autosome Ratio

  8. Transcriptional Regulation As a Result of X:Autosome Ratio NUM:NUM dimers activate transcription of Sxl gene

  9. Post-transcriptional Regulation of Sxl Protein Production

  10. Post-transcriptional Regulation of Tra and Fru Protein Production Sxl Protein Regulates Splicing of tra mRNA

  11. Post-transcriptional Regulation: Alternative Splicing of Tra pre-mRNA Sxl protein may block upstream 3’ splice site

  12. Fru ProteinsControl Sex-Specific Behavior as TranscriptionalRegulators Sxl Protein Regulates Splicing of tra mRNA Tra Proteins RegulateSplicing of fru mRNA Post-transcriptional Regulation of Fru Protein Production

  13. Dsx Proteins Activate or Repress Transcription of Sex-Specific Genes Tra Protein Regulates Splicing of Dsx mRNA Post-Transcriptional Regulation of DSX Protein Production

  14. Summary of Protein Activities Transcriptional Activator Splicing Regulator Splicing Regulator Dsx-M = Transcriptional RepressorDsx-F = Transcriptional Activator Fru-M and Fru-F are Transcriptional Regulators

  15. Development of Anterior-Posterior Body Axis in Drosophila

  16. Gap genes Pair-rule genes Segment-polarity genes Homeotic genes A Hierarchy of Gene Interactions Determines Segment Number and Identity Along the A-P Axis Egg-polarity genes Egg-polarity genes (Maternal) Zygotic genes

  17. Distribution of Egg-polarity Gene Products

  18. Action of Egg-polarity Genes Bicoid and Nanos

  19. Genes Influencing Segmentation along the A-P Axis

  20. Action of Gap Genes Gap gene products divide the body into broad zones for the formation of anteriorposterior segments. Mutations show a loss of specific adjacent segments from region where gap gene is transcribed. Krupple and Knirps encode transcription factors.

  21. Action of Pair-Rule Genes Pair-rule genes divide the body into a series of two-segment units. Pair-rule gene mutations remove alternate segments, either odd or even. Alternating activity of the genes Ftz (stained gray) and Eve (stained brown) is shown. Fushi tarazu (Ftz) and Even-skipped (Eve) encode transcription factors.

  22. Action of Segment-Polarity Genes Segment-polarity genes regulate the organization of subsets of cells within a segment. Segment-polarity mutations cause part of a segment to be deleted and replaced by a mirror image of a different part of the next segment. Engrailed (EN) encodes a transcription factor. Patched encodes a transmembrane protein.

  23. Action of Homeotic Genes Homeotic genes influence the identity of specific segments, controlling the development of segment-specific structures. Mutations cause structures from one segment to develop in another. T3 develops as T2 in the Postbithorax mutation. Pbx is a cis-regulatory region controlling the action of Ubx on T3 development.

  24. Clusters of Homeotic Genes

  25. Antp Scr Ubx Abd-B Order of homeotic genes is colinear with the order of expression along the anterior-posterior axis.

  26. Evolutionary Conservation of Homeotic Gene Regions • Homeotic genes share a 180 base pair region called the homeobox. • The homeobox encodes a DNA-binding domain (homeodomain) with a helix-turn-helix structural motif. • Homeobox regions are found in clustered genes in the mouse.

  27. Homeotic gene mutation resulting in posterior location for anterior structures, i.e. ribs from lumbar vertebrae.

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