Calcium-dependent adhesion is necessary for the maintenance of prosomeres

Cell adhesion has been suggested to function in the establishment and maint enance of the segmental organization of the central nervous system. Here we tested the role of different classes of adhesion molecules in prosencephal ic segmentation. Specifically, we examined the ability of progenitors from different prosomeres to reintegrate and differentiate within various brain regions after selective maintenance or removal of different classes of calc ium-dependent versus -independent surface molecules. This analysis implicat es calcium-dependent adhesion molecules as central to the maintenance of pr osomeres. Only conditions that spared calcium-dependent adhesion systems bu t ablated more general (calcium-independent) adhesion systems resulted in p rosomere-specific integration after transplantation. Among the members of t his class of adhesion molecules, R-cadherin shows a striking pattern of pro someric expression during development. To test whether expression of this m olecule was sufficient to direct progenitor integration to prosomeres expre ssing R-cadherin, we used a retroviral-mediated gain-of-function approach. We found that progenitors originally isolated from prosomere P2 (a region w hich does not express R-cadherin), when forced to express this molecule, ca n now integrate more readily into R-cadherin-expressing regions, such as th e cortex, the ventral thalamus, and the hypothalamus. Nonetheless, our anal ysis suggests that while calcium-dependent molecules are able to direct pro somere-specific integration, they are not sufficient to induce progenitors to change their regional identity. While diencephalic progenitors from R-ca dherin-expressing regions of prosomere 5 could integrate into R-cadherin-ex pressing regions of the cortex, they did not express the cortex-specific ge ne Emx1 or the telencephalic-specific gene Bf-l. Furthermore, diencephalic progenitors that integrate heterotopically into the cortex do not persist p ostnatally, whereas the same progenitors survive and differentiate when the y integrate homotopically into the diencephalon. Together our results impli cate calcium-dependent adhesion molecules as key mediators of prosomeric or ganization but suggest that they are not sufficient to bestow regional iden tities, (C) 2001 Academic Press.