Department of Biology
Memorial University of Newfoundland
Developmental Genetics
is the sub-discipline of genetics
that attempts to reveal the molecular mechanisms
that underpin the events that start with one cell (or a small number
of cells)
and end with a complete organism (or part of one).
Central themes of developmental genetics
1. Building the body plan depends upon Ö
a) Cell fate.
Cell fate is the ultimate differentiated state
to which a cell has become committed.
Developmental field is a group of cells that interact to form a developing
structure (a tissue, an organ or an embryo).
b) Fate refinement.
Cells with a developmental field must be able to identify their location
and make developmental decisions with regard to the decisions of their
neighbouring cells.
c) Totipotent cells have the ability to go through all the stages of
development to produce a normal adult.
d) Cell lineage
The pedigree of cells through the divisions reveals that cells become
more committed to specific cell fates over time.
As cells proliferate in the developing organism, decisions are made
to specify more and more precisely the fate options of cells of a given
lineage
2. Major decisions in building the embryo
a) Separation of the germ line (gamete producing cells) from the soma
(non gamete producing cells)
b) Establishment of the sex of the organism.
c) Establishment of the positional information required to organize
the two major body axis (anterior/posterior [head to tail] and dorsa/ventral
[back to front].
d) Subdivision of of embryonic anterior/posterior axis into a series
of segments or metamers and assignment , based upon location, of distinct
roles to the segments.
e) Subdivision of the embryonic dorsal/ventral axis into the germ layers
(the outer, middle and inner sheets of cells) and assignment of distinct
roles to the germ layers.
f) Production of organs, tissues, systems and appendages through the
interaction of groups of cells from specific segmaental and germ layer
origins.
Among developmental decisions, the simpler ones tend to involve irreversible
commitment to one or two options and complex decisions involve selection
from multiple choices.
3. Regulatory mechanisms and developmental decisions
Often the presence or absence of a given molecule (protein or RNA)
results in the cell or cells taking on one cell fate over another.
This key molecule is referred to as a regulatory binary
switch because it is either "on" or "off" and this leads to a choice
of cell fates.
Off is often the default pathway while on direct the cell into an alternative
pathway.
Once the decision is made, mechanisms lock the decision in place to
ensure continued commitment.
Developmental genetics depends upon various methods of gene
regulation.
a) Transcription initiation.
Transcription factor activation/inactivation can greatly influence
cell fate.
b) Tissue-specific regulation at the level of DNA structure
Somatic changes in gene structure or copy number can be used to regulate
tissue-specific
gene activity.
c) Transcript processing and tissue-specific regulation
The production of an active protein can be regulated by controlling
the pattern of splicing of an initial transcript into a mature mRNA.
Regulatory instructions can be contained with non-protein coding regions
of the mRNAs.
d) Post-translational regulation
After proteins are synthesized, any of a number of events can alter
activity of a protein (cleavage, covalent addition or temporary modifications).
Complex pattern formation and positional information
Mutational analysis (Christiane Nusslein-Volhard and Eric Wieschaus: Nobel
Prize Winners for this work) have revealed both zygotically acting and
maternal effect genes.
The gene bicoid encodes a transcription factor distributed in
an anterioposterior gradient.
This distribution depends upon the localization of the bicoid mRNA
at the anterior tip of the embryo and diffusion
of the protein from this source.
The gene nanos works by a similar in the posterior embryo.
The positional information of the Drosophila A-P axis is generated
by protein gradients dependent upon diffusion of newly made proteins from
the localized mRNAs anchored by binding to the cytoskeleton by the 3'UTRs
of nanos and bicoid.
Positional information can be divided into two classes
Localization of mRNAs and proteins within a
cell.
Formation of a concentration gradient of an extracellular diffusible
molecule which can direct the target cell's fates: a morphogen.
NSERC Undergraduate Student Research Awards Program
Information and
forms for the Summer of 2007 is available here!!!!!
or go to http://www.nserc.ca/ and look for students.
email me at bestave@mun.ca
