How do genetic activities in the mother help the offspring in its development into an adult?
experiments conducted on the fruitfly 15 years ago have done much to advance our understanding of the development of an embryo into an adult. There were two main insights that followed these researches: firstly, that varying levels of protein molecules act as guideposts -- they literally set up a contour map -- in the embryo. Secondly, that many such proteins are created by the mother; they represent the products of genetic activity in her. So, in addition to providing nourishment, the mother also endows her offspring with developmental information. How she does this, however, remains a subject of intense investigation.
Two classes of gene products, messenger ribonucleic acid (m rna ) and proteins -- that are crucial for specifying the head-to-tail body axis in the embryo -- are provided by the bicoid and caudal genes. During the development of the egg in her body (oogenesis), the mother stores bicoid m rna at the front end of the future embryo. Later, this m rna is translated to give a protein product that diffuses along the length of the embryo.
The resulting concentration gradient of bicoid protein (with its highest level near the head and lowest near the back) specifies positions along the head-to-tail axis. Wherever its level is high, bicoid protein activates 'downstream' (genes that act as pathways after other genes) genes; in consequence, genes appropriate to the head and the thorax are 'switched on' in the correct portions of the embryo.
Caudal protein is needed specifically for abdominal development -- for the development of the hind-most structures of the body. However, in contrast to bicoid , the m rna product of the caudal gene is present at an uniform level from front-to-back even though it has maximal activity in the abdominal region.
It turns out that it is the bicoid protein that is responsible for restricting the domain of activity of the caudal product; in the absence of bicoid protein, the caudal concentration gradient is abolished. How does bicoid limit caudal m rna translation to the posterior of the embryo? P D Zamore of the Massa-chusetts Institute of Technology and R Lehmann of the New York University Medical Center -- both in the us -- report on recent experiments that provide a surprising answer ( Current Biology , Vol 6, No 7).
A portion of the bicoid protein contains a homoeodomain, a generic stretch of amino acids that is found in a large number of regulatory genes and is known to bind and influence the activity of specific regions of dna . This bicoid homoeodomain also binds to specific sequences that lie at the end of caudal m rna . Known as 3' utr (3-prime untranslated region), such sequences result from non-coding dna .
But, as is emerging from a host of studies, 3' utr sequences can be quite important in a functional sense. The experiments provide evidence that bicoid homoeodomain binds to caudal 3' utr and represses its translation. Since there is more bicoid protein in the anterior of the egg than in the posterior, it follows that repression is relatively more successful there; resultantly, significant levels of caudal protein are found just where needed -- in the posterior.
The mechanism by which binding of a protein to 3' utr affects m rna translation remains unclear. One model has it that protein binding acts like a glue and converts the m rna into an untranslatable particulate form. But this model has been disproved by an experiment in which an artificial m rna sequence was engineered. The artificial construct encoded two distinct proteins and ended with the caudal 3' utr .
Strangely, bicoid was able to repress translation of the first of the two proteins but not of the second. In any case, evidently the m rna as a whole was not rendered dysfunctional (some portions of the m rna were active, while some were not). While these findings deepen our understanding of how spatial pattern in early development is regulated, at the same time they give rise to questions of how caudal is regulated.
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