RE: Cognitive complexity from so few genes?

From: Rafal Smigrodzki (rms2g@virginia.edu)
Date: Thu Jul 18 2002 - 17:19:16 MDT


It's been some time since I was actively involved in research on the
development of mammalian cortex but let me try to answer some of Emil
Gilliam's questions:

 It is not enough merely to point out the notorious
complexity of protein folding, at least without some good argument about
"how much" of this complexity gives rise to the functional complexity we
see in the mind (or any other organ).

### The complexity of protein folding is only indirectly implicated in the
formation of the brain, in the sense that it merely provides the lower level
building blocks - the direct source or cortical complexity lies higher.

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 I guess what I'm really wondering
is "where" in the genome we can expect to find the difference between
one purported mental module and another, and how this encoding scheme is
not hostile to the evolution of new mental modules by natural selection.

### During ontogeny the cortical sheet is imprinted by concentration
gradients of morphogenetic molecules, such as LAMP, Emx and Dmx gene
products, some members of the FGF family, and doubtlessly many others. The
combinations of morphogene concentrations at particular points on the sheet
direct the neuroblasts to differentiate into module-specific phenotypes.
There is a cascade of such specifying events, starting with the
establishment of main AP and DV axes (initiated by morphogenes acting even
before the formation of the brain), all the way to the subdivision into
single cortical areas. A single morphogen can appear a number of times at
progressively higher levels of differentiation. Thus, even if the number of
true mophogenes was less than a hundred, their spatial and temporal
combination could specify the oft-quoted 10,000 types of neurons. What each
cell does is to integrate chemical (and later - electric) inputs, and
respond with e.g expression of receptors to other morphogens and sending
axons to areas specified by these morphogenes. New modules can be formed if
the response of cells at some point in space (on the cortical sheet) and
time (e.g. 6th month of pregnancy) to the local morphogenes is changed - e.g
a receptor is not expressed (due to a mutation in its promotor), and the
cells instead start responding to competing morphogenes. If the new cortical
area turns out to be doing something useful, the mutation will be favored by
selection.

-----

Since we don't really know, can someone explain at least what we might
expect an answer to this question to look like?

### Hundreds of morphogenes but probably not thousands, with thousands of
possible combinatorial responses encoded in the promotor genes,in the
protein-protein interactions, and other places. Scientists like Pat Levitt,
who discovered LAMP (Limbic Associated Membrane Protein) and in whose lab I
had the privilege to work, have enough to keep them occupied for years to
come.

Rafal



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