Early organogenesis and cell contacts in the proliferating hypophysis of the developing mouse.

The mouse foetal hypophysis which contains the diencephalic downgrowth (Dd) and Rathke's pouch (Rp) was examined using morphological and immunocyto/histo-chemical methods to study the cell-cell and cell-extracellular matrix (ECM) interactions that occur during early organogenesis. While many studies have described that the differentiation of ACTH cells precedes the proliferation of other endocrine cells in the Rp, light and conventional transmission electron microscopic (TEM) investigations have failed to differentiate between the various endocrine cell types in the proliferating distal lobe at the late mid-foetal stage. Conversely, TEM studies have shown that the occurrence of dense secretory vesicles in glandular cells of the presumptive pars intermedia in close apposition with the presumptive neural lobe by a basal lamina, is the earliest sign of endocrine activity in the foetal hypophysis. However, a confocal laser scanning microscopy (CLSM) and fine structure study did not observe direct cell-to-cell contacts between the Dd, Rp and their associated mesenchyme at the late mid-foetal stage. Using CLSM and TEM, we detected active cell turnover with programmed cell death in the proliferating Rp, Dd and their associated cephalic mesenchyme. Morphological findings indicated that apoptosis in the cephalic mesenchyme subsequently brings neurohypophyseal pituicytes and adenohypophyseal precursor stem cells into closer proximity, and alternations in the boundary cell surfaces might initiate signal transduction mediated via the intervening ECM at the proliferation stage.