Download 19) Differential Gene expression in Development

10.0 Introduction to development
Related Sadava’s chapters:
•  19) Differential Gene expression
in Development
•  20) Development and
Evolutionary Change
10.1 Differential Gene expression in Development
A child preformed in
the sperm, according
to Harsoeker (1694)
10.1 Differential Gene expression in Development
Four processes of development:
• Determination sets the fate of the cell
• Differentiation is the process by which
different types of cells arise
• Morphogenesis is the organization and
spatial distribution of differentiated cells
• Growth is an increase in body size by
cell division and cell expansion
10.1 Differential Gene expression in Development
Determination and differentiation occur
largely because of differential gene
expression.
Cells in the early embryo arise from
repeated mitoses and soon begin to
differ in terms of which of which genes
are expressed.
10.1 Differential Gene expression in Development
Morphogenesis also involves differential
gene expression and can occur in
several ways:
• Cell division
• Cell movements
•  Apoptosis (programmed cell death)
•  Growth occurs by increasing the number of
cells or enlargement of existing cells.
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
Cell fate: Type of cell it will ultimately become; a
function of differential gene expression and
morphogenesis.
Experiments in which specific cells of an early embryo
are grafted to new positions on another embryo show
the role of morphogenesis.
As development proceeds, the potential of cells
becomes more restricted.
Cell fate is also influenced by the extracellular
environment, as well as changes in gene expression.
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
A zygote is totipotent: It can give rise to
every cell type in the adult body.
Later in development, the cells lose
totipotency and become determined.
Determination is followed by
differentiation.
For a long time, it has been thought that
differentiation is irreversible. However,
most cells retain the entire genome.
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
In mammals, stem cells occur in tissues that
require frequent replacement—skin, blood,
intestinal lining.
Adult stem cells are multipotent: They produce
daughter cells that differentiate into a few cell
types:
•  Hematopoietic stem cells produce red and white blood
cells.
•  Mesenchymal stem cells produce bone and connective
tissue cells.
10.1 Differential Gene expression in Development
Pluripotent cells in the blastocyst
embryonic stage retain the ability to
form all of the cells in the body.
In mice, these embryonic stem cells
(ESCs) can be removed from the
blastocyst and grown in laboratory
culture almost indefinitely.
10.1 Differential Gene expression in Development
Pattern formation: The process that
results in the spatial organization of
tissues.
Linked with morphogenesis.
Programmed cell death—apoptosis—is
also important. Many cells and
structures form and then disappear
during development.
10.1 Differential Gene expression in Development
In early human embryos, connective
tissue links the fingers and toes. Later,
the cells between the digits die.
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
Polarity was demonstrated using sea
urchin embryos.
If an eight-cell embryo is cut vertically, it
develops into two small larvae.
If the eight-cell embryo is cut
horizontally, the bottom develops into
a larva, the top remains embryonic.
Cytoplasmic determinants are
distributed unequally in the egg
cytoplasm.
These materials play a role in
development of many animals.
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
Segmentation genes determine
properties of the larval segments.
Three classes of genes act in sequence:
•  Gap genes organize broad areas
•  Pair rule genes divide embryo into
units of two segments each
•  Segment polarity genes determine
boundaries and anterior-posterior
organization in individual segments
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
How to establish a protein gradient?
10.1 Differential Gene expression in Development
Maternal effect genes are transcribed in
the cells of the ovary that surround the
egg.
Bicoid and Nanos determine the anteriorposterior axis. Their mRNAs become
localized at both ends of the embryo.
Bicoid protein diffuses away from the
anterior end, establishing a gradient.
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
How to establish regional domains of expression
10.1 Differential Gene expression in Development
At sufficient concentration, bicoid
stimulates transcription of the
Hunchback gene. A gradient of that
protein establishes the head.
Nanos mRNA is transported to the
posterior end. Nanos protein inhibits
translation of Hunchback.
10.1 Differential Gene expression in Development
Fate of a cell is determined by its history
and where the cell is.
Positional information may come in the
form an inducer, a morphogen, which
diffuses from one group of cells to
another, setting up a concentration
gradient.
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
How to establish a stripped pattern?
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
How to specify regional identity
10.1 Differential Gene expression in Development
• Homeotic genes are expressed in
overlapping patterns along the length of
the embryo.
• Each segment expresses a specific
combination of genes. They will
determine what each segment will
become.
• Hox genes are on chromosome 3, in
two clusters, in the same order as their
anterior limit of expression
10.1 Differential Gene expression in Development
10.1 Differential Gene expression in Development
Antennapedia gain-of-function
Bithorax loss-of-function
10.1 Differential Gene expression in Development
Homeotic genes share a 180-bp sequence, the
homeobox, that encodes a 60-amino acid sequence
called the homeodomain.
The homeodomain binds to a specific DNA sequence
in the vicinity of target genes and homeotic proteins
are transcription factors
10.2 Development and Evolutionary change
•  The molecular pathways that determine different
developmental processes operate independently
from one another. This is called modularity
•  Changes in location and timing of expression of
particular genes are important in the evolution of new
body forms and structures
•  Much of morphological evolution occurs by
modifications of existing development genes and
regulatory sequences
•  Mechanisms of development have often evolved to
be responsive to environmental conditions
10.2 Development and Evolutionary change
• The Hox gene cluster is an example of
homology in genes.
• They provide positional information and
control pattern formation in early
Drosophila embryos.
• Hox genes have homologs in mammals,
and the genes are arranged in similar
clusters and expressed in similar
patterns in the embryos.
10.2 Development and Evolutionary change
10.2 Development and Evolutionary change
• The number of Hox genes is limited in
each species (<40).
• Corresponding genes in two clusters in
the same species are called paralogous
• Homologous genes between two
species are called orthologous
• In addition, the homeobox is found in
numerous other transcription factors,
including some from plants.
10.2 Development and Evolutionary change
10.2 Development and Evolutionary change
10.2 Development and Evolutionary change
10.2 Development and Evolutionary change
Genetic switches that determine where and when
genes are expressed underlie both development and
the evolution of differences among species.
In centipedes, Ubx protein activates expression of the
Dll gene to promote the formation of legs.
In insects, a change in the Ubx gene results in a
modified Ubx protein that represses Dll expression in
abdominal segments, so leg formation is inhibited.
10.2 Development and Evolutionary change
10.2 Development and Evolutionary change
Similar processes govern development of
the vertebral column.
Vertebral column has anterior-to-posterior
regions (cervical, thoracic, lumbar,
caudal). The regions are controlled by Hox
genes.
The characteristic numbers of vertebrae in
different species result from genetic
changes that expand or contract the
expression domain of different Hox genes.
10.2 Development and Evolutionary change
10.2 Development and Evolutionary change
Modularity also allows the timing of developmental
processes to be independent—heterochrony.
The neck vertebrae of giraffes are much longer than
those of other mammals.
Bone growth is stopped by a signal that results in death
of chondrocytes (cartilage-producing cells) and
calcification of the bone matrix.
In giraffes this signaling process is delayed in the neck
vertebrae, and they grow longer.
Thus, the evolution of longer necks resulted from
changes in the timing of gene expression.
10.2 Development and Evolutionary change