Segmentation Genes

1
Segmentation Genes And Homeotic
Genes
Larval and adult segmentation
2
Drosophila Development Anterior/Posterior
Axis specified during Oogenesis
Nucleus synthesizes Gurken protein binds to
Torpedo receptor
Secrete molecule which activates protein
kinase A
Microtubules oriented so growing end is at the
posterior
Secreted by Nurse cells
Polarity Established
bicoid mRNA binds to dynein on oskar
mRNA binds to kinesin I and moves microtubules
and moves anteriorally posteriorally (bind to
actin microfilaments)
Fig. 9.08, Pg. 260
3
Unequal distribution of maternal mRNA in eggs
- Translation establishes a protein gradient
across the egg leading to segmentation
A P
Bicoid
Hunchback / Krüppel
Fushi tarazu
Monoclonal Abs against specific maternal
gene products tagged with fluorescent dyes
Engrailed
Fig. 9.17, pg. 267
4
Early Insect Egg
Bicoid mRNA
Posterior
Anterior
No Middle Segments
Destroy RNA with UV light ------ no anterior
structures
5
Maternal effects genes
Nanos Caudal Blocks Hunchback
Bicoid Represses Caudal
Activates Hunchback
A P
Activates Knirps Giant
Developmental Fate
Segmentation
Fig. 9.17, pg. 267
6
Maternal caudal RNA
Ovulation/ Fertilization
Fig. 9.19, pg. 268-269
7
Nanos regulation of Hunchback mRNA translation
Fig. 9.21, pg. 271
8
Ovulation/ Fertilization
Zygotic Gene Expression
Fig. 9.19, pg. 268-269
9
Fig. 9.22, pg. 272
10
Maternal effects genes
A P
Bicoid Hunchback Kruppel / Knirps /
Giant Eve/Ftz Engrailed / Hedgehog
Nanos Caudal
Developmental Fate
Segmentation
Fig. 9.17, pg. 267
11
Gap gene regulation of Pair-rule genes
Concentration gradients of gap genes define
even-skipped pair-rule gene (Eve)
expression Regulation at the level of the
enhancer sites with stimulation inhibition
Activator sites linked to Repressor sites
Competitive interactions
A protein that is a repressor for one stripe may
be an activator for another stripe
Fig. 9.30, pg. 279
12
Promoter Region for Even-skipped (Eve) gene for
Different Stripes Pair rule genes which are
responsible for first identifiable segmentation
Fig. 9.29, pg. 278
13
Transcription of the fushi tarazu Pair-rule gene

• Expression of ftz gene
• diffuse and then enhanced
• into pattern of stripes while
• inhibited in adjacent regions

ftz
eve
Double labeling shows interdigitation of eve and
ftz expression
Fig. 9.32, Pg. 280
14
Pair rules genes Segment polarity genes
Slp
Slp
Slp
Parasegment posterior region of one segment and
anterior region of another Boundaries of
transegmental unit defines segmentation by
defining gene expression
Fig. 9.33, Pg. 282
15
Segmentation polarity genes
Segment polarity genes
Pair-rule cells having Eve or Ftz proteins are
competent to express Engrailed gene
(En) Engrailed protein activates transcription
of hedgehog gene Hedgehog binds to patched
receptor preventing patched protein from
inhibiting signaling from smoothened protein
Inhibits inhibitor
Fig. 9.33, pg. 282
16
Hedgehog Signal Transduction Pathway
Smoothened protein releases Ci
Ci Cubitus interruptus cleaved in
to transcriptional repressor
Fig. 6.17, pg. 153
17
Wingless/Hedgehog Signaling Center
Fig. 9.34, pg. 283
18
Evolutionary conservation of homeotic
gene organization
It is known that nature works constantly with
the same materials. She is ingenious to vary
only the forms. As if, in fact, she were
restricted to the same primitive ideas, one sees
her tend always to cause the same elements to
reappear, in the same circumstances, and with the
same connections. E. Geoffroy
Saint-Hilaire 1807
19
Homeotic Selector Genes
Specification of segment structures
In situ hybridization for 4 genes
Fig. 9.35, Pg. 283
20
Helix 3 of homeodomain binds in DNA groove (60
a.a.)
Homeobox DNA sequence within homeotic genes
that codes for a 60 a.a. domain of a homeodomain
protein Homeodomain proteins are a family of
transcription factors characterized by a 60 a.a.
domain that binds to DNA at promoter and/or
enhancer sites
Fig. 9.40, Pg. 287
21
Homeotic Gene Expression
En
Ubx
Dl
Antp
Fig. 9.35, pg. 283
22
Homeotic genes activate/repress realisator genes
Antennapedia gene expressed in T2 binds to and
represses enhancer regulating genes for antenna
and eye development
Wingless gene expressed in T2 wingless protein
acts as a growth factor to promote cell
proliferation that extends the wing and
establishes proximal/distal axis of the wing
23

• Target specific
• homeotic genes
• for expression

Ultrabithorax gene mutation transforms 3rd
thoracic segment into another 2nd thoracic
segment