Variations in the structure of the neocortex induced by single gene mutatio
ns may be extreme or subtle. They differ from Variations in neocortical str
ucture encountered across and within species in that these "normal" structu
ral variations are adaptive (both structurally and behaviorally), whereas t
hose associated with disorders of development are not. Here we propose that
they also differ in principle in that they represent disruptions of molecu
lar mechanisms that are not normally regulatory to variations in the histog
enetic sequence. We propose an algorithm for the operation of the neuronoge
netic sequence in relation to the overall neocortical histogenetic sequence
and highlight the restriction point of the G1 phase of the cell cycle as t
he master regulatory control point for normal coordinate structural variati
on across species and importantly within species. From considerations based
on the anatomic evidence from neocortical malformation in humans, we illus
trate in principle how this overall sequence appears to be disrupted by mol
ecular biological linkages operating principally outside the control mechan
isms responsible for the normal structural variation of the neocortex. (C)
2000 Wiley-Liss, Inc.