Developmental Genetics How Selective Gene Expression Determines the Developmental Fate of Specific Cells -Chapter 16, pages Chapter 21, pages

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

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

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

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

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

Effects of X:Autosome Ratio

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

Post-transcriptional Regulation of Sxl Protein Production

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

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

Post-transcriptional Regulation of Fru Protein Production Sxl Protein Regulates Splicing of tra mRNA Tra Proteins Regulate Splicing of fru mRNA Fru Proteins Control Sex-Specific Behavior as Transcriptional Regulators Nervous system processing of information from antennae Courtship Song Abdomen Movement

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

Summary of Protein Activities NUM:NUM Homodimers NUM = numerator Sxl = Sex Lethal Tra = Transformer Dsx = Double sex Fru = Fruitless Transcriptional Activator Splicing Regulator Dsx-M = Transcriptional Repressor Dsx-F = Transcriptional Activator Fru-M and Fru-F are Transcriptional Regulators

Development of Anterior- Posterior Body Axis in Drosophila

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

Distribution of Egg-polarity Gene Products

Action of Egg-polarity Genes Bicoid and Nanos Bicoid ant  post Transcriptional activator of anterior- specific genes, including hunchback, a gene needed of head and thorax development Nanos post  ant Translational repressor of hunchback, preventing expression of anterior structures

Genes Influencing Segmentation along the A-P Axis

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.

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.

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.

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.

Clusters of Homeotic Genes Cluster Affects Structures Developing in Genes Antennapedia Complex Head and Anterior Thoracic Regions Antennapedia Scr Bithorax Complex Abdomen and Posterior Thoracic Regions Ultrabithorax Abdominal-A Abdominal-B

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

Evolutionary Conservation of Homeotic Gene Regions Homeotic genes share a 180 base pair region called the homeobox.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.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.Homeobox regions are found in clustered genes in the mouse.

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