Lecture 11: Gap Gene Function and the Control of Pair Rule and Homeotic Selector Genes

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Lecture 11 Gap Gene Function and the Control of
Pair Rule and Homeotic Selector Genes
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Gap Gene Function

• Gap genes directly activate
• i) Pair Rule genes
• ii) homeotic selector genes

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Pair Rule genes

• 1. An embryo homozygous for a loss-of function
  mutation in a pair rule gene lacks every other
  segment. The role of the gene is to promote
  segment formation.

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Pair Rule genes

• Several pair rule genes have been cloned and all
  encode transcription factors.
• 3. The pair rule genes are first expressed in the
  cellular blastoderm in seven stripes, 3-4 cells
  wide and perpendicular to the anterior-posterior
  axis. Stripes of expression are separated by a
  3-4 cell wide stripe of no expression. The total
  number of stripes (expression no expression)
  correspond to the number of segments (14).

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The expression pattern of the primary pair rule
genes is established by the gap gene
transcription factors. How?

• 1. Pair rule genes must be activated by a
  combination of the gap gene morphogens.
• a) Pair rule genes are expressed after
  blastoderm cellularization within the domains of
  all of the gap genes.
• b) In gap gene mutants the pair rule genes are
  not expressed correctlysome of the stripes of
  expression do not form.

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What is the pattern of Gap gene expression in the
syncytial blastoderm?
hb, Kr and kni are transcribed by contiguous
nuclei in specific regions of the embryo with hb
more anterior to Kr and Kr more anterior to kni.
Gap genes are first expressed 11-13 th cycles of
cell division
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High
Kni protein
Amount of protein
Low
Posterior
Anterior
Pair rule Gene exp.
Position in embryo
eve
odd
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The expression pattern of the primary pair rule
genes is established by the gap gene
transcription factors. How?

• 1. Pair rule genes must be activated by a
  combination of the gap gene morphogens.
• a) Pair rule genes are expressed after
  blastoderm cellularization within the domains of
  all of the gap genes.
• b) In gap gene mutants the pair rule genes are
  not expressed correctlysome of the stripes of
  expression do not form.

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High
Kni protein
Amount of protein
Low
Posterior
Anterior
Pair rule Gene exp.
Position in embryo
eve
odd
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The expression pattern of the primary pair rule
genes is established by the gap gene
transcription factors. How?

• 2. The pair rule enhancer regions are very
  complex involving multiple binding sites for all
  of the gap gene transcription factors. The
  binding of different amounts and combinations of
  gap gene protein to the pair rule promoter result
  in its activation or repression.
• Deletions of parts of the enhancer region of pair
  rule genes can result in the loss of only one or
  two of the stripes.

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Wild type even-skipped gene (structure here is
invented)
enhancer elements
enhancer element
eve gene
P
Exon 2
Exon 3
Exon 1
Specific enhancer elements are recognized by
different combinations of gap morphogens to
produce specific stripes. Deletion of one
element can result in loss of one stripe.
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Gap Gene Function

• Gap genes directly activate
• i) Pair Rule genes
• ii) homeotic selector genes

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GENERAL LESSONS CONCERNING PATTERN FORMATION

• Asymmetry in the female is used to generate
  asymmetry in the oocyte.
• Asymmetry in the oocyte is used to generate
  maternal morphogens in the early embryo.
• Maternal morphogens establish a specific pattern
  of zygotically-expressed morphogens.
• Zygotic morphogens activate a complex set of
  genes required to determine the differential
  fates of cells in the blastoderm thus
  establishing a spatial pattern of morphological
  structures.

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Principles of pattern formation

• 1. Must establish positional information (spatial
  information) within the developing
  embryo(morphogen? environmental signals).
• 2. Direct simple patterns (anteriorposterior,
  dorsal--ventral) early and use to elaborate most
  complex pattern.
• 3. Use a cascade of determination events to
  coordinate timing.
• 4. Use master regulatory proteins each of which
  will be expressed in specific groups of cells
  marking them for a particular fate.