Genetics of Axis Specification in Drosophila: Segmentation Genes

Genetics of Axis Specification in Drosophila: Segmentation

Genes

Gilbert - Chapter 9

Today’s Goals• Describe the use of a Genetic screen to identify

functionality of individual gene products• Identify Eric Weischaus and Christianne Nusslein-

Volhard• Identify key molecular players in establishing polarity

and segments in various types of embryos• Define the term “positional information”• Describe how evolutionarily conserved genes play

similar roles in development of a wide variety of species• Define transcription factor

The Segmentation Genes

• Now we have a mechanism for setting up the Anterior and Posterior ends of the embryo

• BUT- there are many specific segments along the axis of the embryo

• How can segmentation be achieved?– We must also examine the formation of

parasegments– Parasegments make up the segments of the

embryo - embryonic building blocks

Parasegments as defined by denticle pattern

Segmentation Genes

• Three classes of Segmentation genes– Hierarchical arrangement based on what they control– Now - all are zygotic genes (not maternal-effect)

• Gap genes– Divide embryo into broad regions (several

parasegments)

• Pair-rule genes– Divide regions defined by gap genes into smaller

regions (fewer parasegment)

• Segment Polarity genes– Control patterns within each parasegment

Gap Genes

• Ex. Hunchback, Krüppel, knirps• Mutations affect broad areas of the body plan• These genes are activated or repressed by

the maternal effect genes (ex. Bicoid)• Expressed in broad domains along A-P axis• Expression patterns correspond very well with

segments that are lost when mutations occur

Gap Genes

• Example of mutation– Krüppel – Expressed in segments 4-6– Mutant for Krüppel is missing these

segments and those immediately adjacent to them

Gap Genes

• Expression in the embryo changes over the course of development– Begins as low levels across whole embryo– Becomes consolidated into discrete regions within

the embryo– Proteins become localized to specific areas along

axis– Initially controlled by concentration gradients of

maternal effect genes– Expression patterns eventually defined by

interactions with one another

Maternal Effect Genes Influence Gap Genes

• High levels of Bicoid and Hunchback– Induce expression of Giant near the anterior end– Inhibit expression of knirps

• Slightly lower levels of Hunchback– Krüppel expression induced

– More complex - several pathways that lead to activation of genes in multiple places

SO…

• The net result of all of these interactions– Precise expression patterns of overlapping

mRNAs in specific sub-regions of the embryo– Overlap is only 8 cells or so

• GAP genes set up sub-regions of the embryo - not individual segments, but smaller sections than just Anterior-Posterior

Pair-rule Genes

• Begin to define segments• Ex. Fushi tarazu (ftz), hairy, even-skipped

(eve)• Mutation in pair-rule gene deletes every other

parasegment– Ex. Ftz

• At least eight pair-rule genes act to divide the embryo into a series of stripes that overlap

Pair-rule genes

• Expressed in stripes along the embryo that represent the future segmentation of the body

• Gene is transcribed in a vertical stripe of cells, not transcribed in next vertical stripe - continues to alternate along axis

• Divide the embryo into 15 subunits– PHENOMENALLY specific control of

expression of these genes!

• Within these regions, different combinations of gene expression specify both the type of segment that will form and the proper order of segments.

Pair-rule Gene Regulation

• How is the transcription of these genes regulated to appear in alternating stripes of cells?– Appears to be under control of Gap genes– In places where the edges of bands of gap gene

expression overlap (ex. Hunchback with Kruppel) expression of a pair rule gene is activated

– In places where other bands of gap genes overlap, a pair rule gene gets turned off

Pair-rule genes: Summary

• Tight control of expression by enhancer/repressor interactions in the promoter regions results in 7 stripes of each gene

• This divides the embryo into the 14 parasegments along the axis

• Each gene is expressed in different parasegments

• Each parasegment has a different combo of pair-rule genes