Specific chromosome domains in interphase nuclei of neurons and glia were 
studied by three-dimensional (3-D) reconstruction of serial optical sections 
from in situ hybridized human CNS tissue. Overall patterns of centromere 
organization, delineated with alphoid repeats, were comparable to those seen in 
mouse, and are clearly conserved in mammalian evolution. Cloned probes from 
other individual chromosome domains were used to define interphase organization 
more precisely. Homologous chromosomes were spatially separated in nuclei. In 
large neurons, probes specific for 9q12, or 1q12 showed that at least one 
homolog was always compartmentalized together with centromeres on the nucleolus, 
while the second signal either abutted the nucleolus or was on the nuclear 
membrane. A telomeric Yq12 sequence also localized together with perinucleolar 
centromeres in a completely non-Rabl orientation. In astrocytes, these three 
chromosome regions were on the membrane and not necessarily associated with 
nucleoli. Therefore there are different patterns of interphase chromosome 
organization in functionally distinct cell types. In contrast to the above 
domains, a 1p36.3 telomeric sequence embedded in a large Alu-rich and early 
replicating chromosome region, was always found in an interior euchromatic 
nuclear compartment in both neurons and glial cells. In double hybridizations 
with 1q12 and 1p36.3 probes, 1p arms were clearly separated in all cells, and 
arms projected radially into the interior nucleoplasm with non-Rabl 
orientations. There was no absolute or rigid position for each 1p arm with 
respect to each other or to the major dendrite, indicating that individual 
chromosome arms may be dynamically positioned even in highly differentiated cell 
types. We suggest that centromeric and other highly repeated non-transcribed 
sequence domains may act as general organizing centers for cell type specific 
interphase patterns that are conserved in mammalian evolution. Such centers 
would allow selected groups of chromosome arms to extend into (and contract 
from) an interior, presumably transcriptionally active, nuclear compartment.