6 and 8 November, 2006

Chapter 18

Gene Regulation During Development

Overview• Differences in cell type are fundamentally differences in gene expression.• These expression differences are often monitored using microarray hybridization.• Differential gene expression is initiated by asymmetrical mRNA distribution, cell-

cell contact, or by diffusible signals.• Gradients of signaling molecules can give location information to cells.• Asymmetrically distributed mRNAs use the cytoskeleton for localization.• Drosophila embryogenesis is a well-understood system of animal development.• A morphogen gradient controls dorsal-ventral orientation in Drosophila.• Asymmetrically distributed mRNAs control anterior-posterior orientation and

ultimately segmentation.• Segmentation also depends on the interplay of regulators at the control regions of

genes.• Bioinformatics tools are useful in identifying genes that are developmentally

regulated.

Signaling Differentiation

Transducing the Signal

Regualtion in a

Morphogen Gradient

Regulation by Asymmetrically Distributed mRNA

Regulation by Asymmetrically Distributed mRNA

Polar Cytoskeletal Elements

Regulation by Cell-cell contact in B. subtilis

Regulation by Cell-cell contact in Animal

Development

Regulation by Cell-cell contact in Animal

Development

Morphogen Gradient

Drosophila Development

Spätzle-Toll create a gradient of Dorsal in nuclei.

Transcriptional response to the Dorsal Gradient

Snail keeps rhomboid off in cells of the mesoderm.

Polar Distribution of

bicoid and oksar in

Drosophila Embryos

Bicoid regulates orthodenticle and zygotic hunchback.

Maternal hunchback mRNA is evenly distributed, but translationally repressed by the posteriorly

concentrated nanos.

The hunchback gradient regulates gap genes as a transcriptional repressor.

Gap genes direct the

expression of pair-rule genes.

Gap genes direct the

expression of pair-rule

genes.

Bioinformatics and the identification of enhancers.

Competition and Quecnching in the eve enhancer

Repression of eve-3 and eve-4 enhancers by hunchback and knirps.

Enhancer autonomy requires short-range repression.

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