On Feb 23 J.Edser wrote:>NC:-
>I agree with you that from a single case of epigenetic control of the
>expression of melatonin genes in the pineal cells one may not conclude the
>existence of the epigenetic system of inheritance predicted already by
>J.Maynard Smith. But would you agree with me that the existence of an
>epigenetic system of inheritance could not be reasonably denied if
>1. The epigenetic control of the expression of nonhousekeeping genes proves
>to
>be a general mode of expression of (nonhousekeeping) genes in the CNS, and
>2. The expression of nonhousekeeping genes in extraneural cells is
>epigenetically regulated by signals from the CNS?
>
>JE:-
>I agree that the CNS can control gene expression.
>However, that is different to suggesting that the
>CNS provides a verified heritable epigenetic platform from
>which to do this. The problem is that very little will
>seems to exist to explore such a possibility. Can the CNS
>provide substances that can move into egg and/or sperm cells
>that could alter, when, by how much, and which genes are
>expressed within each offspring? It seems to me that
>such substances, if they existed, would be of enormous benefit
>and would most probably be proteins. Because proteins can be
>coded by DNA/RNA does not mean that they cannot be
>regarded as epigenetic in their own right. Such a
>epigenetic system would act something like Darwin's pangenes.
>Substances that control gene expression that have been
>fine tuned to the parental environment could be passed on to
>offspring who are born and develop already fine tuned to the
>immediate parental environment in which they will probably
>find themselves, giving them a selective edge. In some species
>the primordial germ cells
>Of course this does not stop these offspring doing their
>own fine tuning and passing this on to their offspring.
>Heritable epigenetic control systems would mostly
>remain much more flexible than genetic control
>systems because immediate environments can quickly
>change. It seems reasonable to suppose that
>the more rigid genetic system working alongside a more
>flexible epigenetic system allows much more efficient long
>and short term adaptation.


While you agree that the CNS can control gene expression (and I expect you also
to agree that it DOES that), you question whether this epigenetic control might
represent a general mechanism of gene expression in metazoans.

My answer would be "Yes", but I know I need to elaborate on this and I will
within the limits of this newsgroup.

As we all know, from 10-30,000 genes of the metazoan genome, several thousands,
the so-called HOUSEKEEPING GENES,  are needed for the subsistence and
reproduction of metazoan cells and are expressed some time during the lifetime
of the cell. The rest, i.e. the majority of them are NONHOUSEKEEPING GENES,
which perform extracellular, organismic functions and are expressed
differentially in different types of cells. Their extracellular function
determines the extracellular origin of signals for their expression, for no
cell could figure out what the organism might need at any particular point in
time (cell-cell interactions come to mind but they will later be dealt with).

But the extracellular signals (protein- and nuclear hormones, growth factors,
other secreted proteins and even neuropeptides, neurotransmitters and
neuromodulators) are themselves produced in response to upstream signals
(hormones of the target endocrine glands in the case of growth factors). For
almost a century it is known that those glands produce their hormones in
response to specific hormones produced by the pituitary that was considered to
be the "master gland". After 50-60es of the last century
biologists have shown
that the pituitary, as well, synthesizes each of its hormones in response to a
specific "releasing" hormone produced by a part of the brain, the
hypothalamus.
During the last two decades evidence is accumulating that shows that the signal
cascade for expression of the hypothalamic genes starts still higher (or
deeper) in the brain with the chemical output (signals) that neural circuits
produce by processing (a computational, nongenetic process) of interna/external
stimuli.

This mechanism of gene activation in the CNS makes possible a flexible and
manipulative expression of genes that could otherwise not be expressed. The
need for this manipulative expression of genes might have determined the
evolution of  blood-brain barrier; the CNS does not need to have contact with
most of the circulating signal molecules. What it needs is information on the
presence and/or level of the signal molecules (the pervasive presence of the
neural tissue in the body allows this) which is used  to "calculate" the
necessary  response, that is release of a chemical signal that leads to the
expression of a gene that the signal.
molecule itself can not express. So, e.g. a the estradiol does not have access
to the hypothalamus, but a change in its level is "perceived'" by the CNS,
which by processing this stimulus makes possible expression of the GnRH gene
(not genes that it activates in  nonneural cells, such as cyclin D, IGF-1
etc.). This is clearly a manipulative expression of genes that is made possible
by the processing of a stimulus in a specific neural circuit.

I admit that  by showing that epigenetic information generated in the CNS
regulates gene expression we have not  proven the existence of what you call
"heritable epigenetic platform" for as you point out, this would
require the
CNS to "provide substances that can move into the egg and/or sperm cells that
could alter, when, by how much, and which genes are  expressed within each
offspring."

What we need to demonstrate is that all the stages of animal reproduction,
starting with the formation of gametes and  individual development are under
the 
CNS control and regulation.

Adequate experimental evidence already shows that the CNS (to be more exact,
the integrated control system, which besides the CNS comprises the mechanisms
for monitoring the status of the living system in general as well as the
pathways for transmission to the cells all over the animal body of the
epigenetic information  generated in neural circuits) controls and regulates:

1. The formation of the egg and sperm cells

2. The placement of maternal cytoplasmic factors in the egg cell.

3. The early embryonic development (which is regulated not by zygotic genes,
but by maternal cytoplasmic factors) up to the phylotypic stage, when a
functioning CNS first arises.

4.The postphylotypic development, including the post-natal development (the
development of secondary sexual characters etc.).
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