Transcript Homeobox Genes - SCIENCE AT SKINNERS

Homeobox Genes
Body organisation
Cell Differentiation
• Cell differentiation is the development of
non-specialised cells into cells with specialised
functions.
– Examples: muscle cells, liver cell, red blood cells
• As organisms grow and develop from fertilised
eggs; organs and tissues develop to produce a
characteristic form. The process is called
morphogenesis.
• Both processes are controlled by gene
expression
What is gene expression?
Gene expression is the
activation of a gene that
results in a polypeptide or
protein being made.
The expression of some
genes (regulatory genes)
results in the production
of a protein that can turn
on or switch off other
genes, these are called
Transcription factors
Body plans
• Every organism has a unique body pattern
because of the influence of HOMEOTIC genes.
• These specify how different areas of the body
develop their individual structures, eg. Arms, legs
etc
• HOMEOTIC or HOMEOBOX genes were
discovered when geneticists studying fruit flies
found mutants with legs growing where their
antennae should be and 2 sets of wings instead of
1.
Homeotic Genes
• Homeotic genes are regulatory genes that
determine where certain anatomical
structures, such as appendages, will
develop in an organism during
morphogenesis.
• These seem to be the master genes of
development, they act as switches for
other genes
• Mutant Antennapedia gene
Normal
Mutant with legs growing out
of head
• Antennapedia complex (group of Homeobox genes)
• 5 genes that affect the anterior part of the fly
• When mutated, legs grow in the place of antennae
• Bithorax gene complex (3 homeobox genes affecting
thoracic development)
a. Normal – wings on 2nd thoracic segment and 2
halteres on 3rd thoracic segment (far left photo, halteres in
white)
b. Mutant – 3rd segment has wings so 2 sets of wings
and no halteres
Halteres
7
Homeobox
• In Drosophila (fruit flies) the
specific DNA sequence within
a homeotic gene that
regulates patterns of
development is the
homeobox.
• The same or very similar
homeobox sequences have
been found in many other
eukaryotic organisms
• Homeotic genes code for
homeotic proteins that function as
transcription factors which switch
on other genes
• The Homeobox is a DNA sequence
within the homeotic genes which
contains 180 base-pair sequences,
coding for a 60 amino acid
polypeptide.
• The protein binds to an area of the
DNA and initiates the transcription
of another set of genes. It acts like
a switch.
Homeobox (HOX genes)
The HOX genes encode important transcription factors. The transcription
factors cause proteins to be made that specify cell fate and identify
– the embryonic pattern along the primary axis (anterior/posterior)
– as well as the secondary axis (genital and limb bud)
– They have a major role in development of CNS, axial skeleton, positioning of
limbs as well as the gastrointestinal and urogenital tract.
Homeotic genes involved in spatial pattern control and development contain a
conserved 180-bp sequence known as homeobox. This encodes a 60-aminoacid domain that binds to DNA.
– The Hox proteins regulate other “executive” genes that encode transcription
factors or morphogen signals, as well as operating at many other levels, on
genes that mediate cell adhesion, cell division rates, cell death and cell
movement.
In Humans as in most vertebrates there are 4 homeobox gene clusters (39 HOX
genes), located on chromosomes 7p14, 17q21, 12q13 and 7q31.
Drosophila has eight Hox genes arranged in 2 clusters on a single chromosome.
A. Drosophila's eight Hox genes in a single cluster and 39 HOX genes in humans.
B. Expression patterns of Hox and HOX genes along the anterior-posterior axis in
invertebrates and vertebrates.
Hox genes
• Three lines of evidence support the idea that
Hox gene complexity has been instrumental in
the evolution and speciation of animals with
different body patterns
1. Hox genes are known to control body
development
2. General trend for simpler animals to have fewer
Hox genes and Hox gene clusters
3. Comparison of Hox gene evolution and animal
evolution bear striking parallel
Hox genes
• Found in all animals
• Genetic mutation of Hox genes may have been
critical events in the formation of new body
plans
• Number and arrangement of Hox genes varies
among different types of animals
• Increases in the number of Hox genes may
have led to greater complexity in body
structure
Hox genes in the Animal Kingdom
• Fruit flies have only one
Antennepedia-bithorax
complex
• Humans and many other
vertebrates have 4 similar
Hox gene clusters
• They probably arose
through gene duplication
• Hox genes shape the
number and appearance of
body segments (repeated
structures) along the main
body axes of both
vertebrates and
invertebrates
How is a multicellular organism made?
• See Page 114 Text book
•Even before fertilisation an egg has a gradient of proteins that help to establish
its polarity (which end becomes the head or anterior and which is the tail,
posterior)
•After fertilisation “Maternal Effect” genes cause more proteins to be made that
reinforce this polarity and also establish the dorsal (back) and ventral (belly)
orientation
•Polarity is this formation of the axis on which the embryo differentiates
• Once the orientation is in place other genes are switched on
•Segmentation occurs driven by Segmentation genes
•Finally the Homeotic Selector genes are switched on
•These control the final specialised development of each segment
•There are two gene families in fruit flies (Drosophila), one controls the
development of head and thorax, the other controls the development of thorax
and abdomen
Drosophila development
•
•
•
The fertilised egg establishes
the pattern for the adult body
plan by establishing protein
gradients. (a)
After fertilization, the zygote
develops into a blastoderm.
A series of nuclear divisions
without cytoplasmic division
produces many free nuclei in a
syncytial blastoderm (b and c)
Individual cells are created
after the nuclei line up along
cell membrane to form a
cellular blastoderm (d)
See page 114
Gastrulation involves cells migrating to
the interior, 3 cell layers formedectoderm, mesoderm and endoderm (e)
Segmented body plan develops (f) driven by
segmentation genes
Md, Mx and Lb segments merge to form
head
3 thoracic segments T1-3
8 abdominal segments A1-8
Larva – free living
Pupa – undergoes metamorphosis
Adult form determined by expression of
Homeotic selector genes
Egg to adult in 10 days
A Homologous Group of Homeotic Genes Is
Found in All Animals
• Vertebrate Hox genes are homologous to those
that control development in simpler organisms
such as Drosophila
• Homologous genes are evolutionarily derived
from the same ancestral gene and have similar
DNA sequences
• Hox genes in mice
1. Follow the colinearity rule (are expressed in the
same sequence as in simpler animals)
2. Have a key role in establishing anteroposterior
axis and controlling the development of the body
plan
Homeotic genes in Mus
• The mouse has
Hox genes on 4
different
chromosomes
• Hox genes are
similar to those
found in
invertebrates but
spread across
more
chromosomes
Four general phases for
body formation
1. Organize body
along major axes
2. Organize into
smaller regions
(organs, legs)
3. Cells organize to
produce body
parts
4. Cells themselves
change
morphologies
and become
differentiated
Hox genes determine the number and types of
vertebrae in animals
• Hox c-6 determines that the chicken has a shortish neck and
the 7 vertebrae shown will develop ribs
• Snake: Hox c-6 is expanded dramatically toward the head and
toward the rear so the snake has no neck and all these
vertebrae develop ribs.
Positional information during
development
• Each cell in the body must
become the appropriate cell
type based on its relative
position.
• Each cell receives positional
information that tells it where
to go and what to become.
• Cells may respond by
1. Cell division,
2. cell migration,
3. cell differentiation or
4. cell death (apoptosis)
See pages 116117 for details
of Apoptosis
Position or Spatial Organization is Everything
• 2 main mechanisms are used to communicate positional
information
• Morphogens , eg retinoic acid; this activates homeobox genes in the
correct sequence. High concentrations of Vitamin A(precursor to
retinoic acid) taken in pregnancy can interfere with the correct
sequence of homeobox activation and hence affect the
development of the embryo and cause birth defects
• Cell adhesion
Cell adhesion
• Each cell makes its own cell adhesion molecules
(CAMs)
• Positioning of a cell within a multicellular organism is
strongly influenced by the combination of contacts it
makes with other cells and with the extracellular
matrix.
For more information go to:
• http://www.pbs.org/wgbh/evolution/library/0
3/4/l_034_04.html
• http://www.dnaftb.org/dnaftb/37/concept/in
dex.html
• http://learn.genetics.utah.edu/archive/bodyp
atterns/index.html
• Or search for information yourself!