Morphogenesis of branching tubules in cultures of cloned mammary epithelial cells

Abstract

Morphogenesis (the development of biological form, usually of multicellular organisms or their parts) is generally studied in simple organisms like the slime mould Dictyostelium¹, for in mammals even single tissues like the mammary epithelium discussed here appear complex. Mammary epithelium, supported by mesenchymal tissue, forms a system of branching, tubular ducts. During phases of rapid growth these ducts end in solid, swollen ‘end-buds’, and when mature in globular ‘alveoli’². The mesenchyme influences the morphogenesis of the epithelium and may be essential for this process^3,4. An unknown number of cell types are present in both the epithelium and the mesenchyme. One step towards a better-defined ‘model gland’ was taken by Yang et al.⁵, who recently described three-dimensional, solid, tumour-like outgrowths from clumps of mouse mammary tumour cells cultured in floating ‘collagen gel’⁶ instead of on a plastic surface. I now describe behaviour retaining some elements of natural morphogenesis, in a cloned line of epithelial cells and thus in the unequivocal absence of mammary mesenchyme—unless mesenchyme can arise from epithelium. On floating collagen gel Rama 25 cells (derived from a rat mammary tumour⁷) could generate three-dimensional structures which, although often disorganized and tumour-like, included branching, hollow tubules, sometimes with bulbous ends. Thus all the information to specify such organization resided in a single cell type and survived cloning. This raises the possibility of a simple mammalian system in which morphogenetic mechanisms, and their relation to cell differentiation, can be studied as readily as in Dictyostelium.