THYROTROPIN INHIBITS THE INTRINSIC LOCOMOTILITY OF THYROID-CELLS ORGANIZED AS FOLLICLES IN PRIMARY CULTURE

The regulation of cell locomotion is a fundamental determinant of tiss ue architecture, Even in solid tissues of adult organisms cells often retain an intrinsic locomotor capacity which is activated during wound healing or tumor metastasis. In this study we have examined the role of cell locomotion in an in vitro model of thyroid epithelial pattern generation. Primary cultures of adult porcine thyroid cells reorganize to form follicles within three-dimensional cell aggregates when stimu lated by thyrotropin (thyroid-stimulating hormone, TSH). Removal of TS H from the culture medium caused established follicles to reorganize i nto a confluent, two-dimensional epithelioid monolayer. The earliest o bserved change was the appearance of spreading cells at the peripherie s of aggregates. These cells displayed broad lamellipodia whose format ion was associated with the redistribution of microfilaments and micro tubules and the accumulation of myosin. Spreading cells could migrate into, and fill, artificial wounds several millimeters wide without evi dence of cell proliferation, indicating that cells became locomotile a s they spread from follicles to form monolayer. Both spreading and mig ration were inhibited by cytochalasin B. In contrast, cells spread in the presence of colchine, but failed to migrate subsequently. Thyroid cell locomotility from follicles was inhibited by TSH, a cAMP analog, and a cell-free membrane fraction. However, migration from established monolayer cultures was not affected by these regulatory agents. This indicated that cell spreading was an important regulatory locus in thy roid cell patterning. We conclude that the tonic inhibition of thyroid cell locomotility contributes to the maintenance of follicular archit ecture in vitro. TSH and cell-cell contact may inhibit locomotion by p reventing follicular cells from spreading, the earliest step in the mo rphogenetic conversion of follicles to monolayer. (C) 1994 Academic Pr ess, Inc.