We have studied the M cell origin and differentiation pathway in rabbit gut
-associated lymphoid tissues. Micro-dissected domes and epithelium isolated
by ethylene diamine tetra acetic acid detachment allowed us to view the wh
ole epithelial surface from the bottom of crypts to the top of domes. We us
ed monoclonal antibodies specific to the apex of either M cells or dome ent
erocytes, lectins, and antibodies to vimentin in appendix, distal Peyer's p
atches and caecal patches.
The earliest vimentin-labeled M cells were observed in the BrdU-positive pr
oliferative zone of dome-associated crypts, Gradual differentiation of the
M cell vimentin cytoskeleton started at this site to progressively give ris
e to the first pocket-forming M cells in the upper dome. Therefore, these m
itotic cells of the crypts appear as the direct precursors of M cells. In a
ddition to an early appearance of M cell markers, a regular mosaic-like rel
ative distribution of M cells and dome enterocytes was already detected in
the vicinity of crypts, similar to that observed on the lateral surface of
domes where functional M cells lie. This constant distribution implies that
there is no trans-differentiation of enterocytes to M cells along the cryp
t-dome axis, Together, these observations provide very strong evidence in f
avor of an early commitment in crypts of M cell and enterocyte distinct lin
eages.