During organogenesis, the issue of size regulation is as important as shape
and differentiation. We propose that the regulation of the dimensions of t
he epithelium and its appendages (length, width, thickness) are based on re
gulation of cell numbers in specific sites, reflecting the input and output
of cells in that region. This process is in turn regulated by the flow fro
m the domain of proliferating cells to the domain of postmitotic differenti
ated cells. When the homeobox gene Msx-2 is over-expressed in transgenic mi
ce under the control of the CMV promoter, the epidermis is thickened with h
yperproliferation and hyperkeratosis. Hairs are shorter and the matrix regi
on is shrunken. We suggest that Msx-2 may be one of the regulators involved
in the control of organ size, and the above phenotypes are the manifestati
ons of an increased cellular flow from proliferation domain to differentiat
ion domain in the tissue.