The nuclear receptor family of transcription factors contains about 270 members, yet only few of them were assigned to a particular function or developmental process. The nhr-25
gene encodes a nuclear receptor orthologous to transcription factors FTZ-F1 in insects and SF-1/LRH-1 in mammals. NHR-25 is required for embryogenesis, gonad and vulva development and molting [1,2], yet its precise position in any genetic regulatory pathway is currently unknown. To understand how NHR-25 functions, we focused on one aspect of its RNAi phenotype and analyzed the postembryonic NHR-25 action in the hypodermis. Our data suggest two roles for NHR-25: (1) NHR-25 is involved in the acquisition of the hypodermal cell fate during the asymmetric divisions of lateral seam cells. When a strain JR667, marking all lateral seam cell nuclei with GFP, was subjected to nhr-25
RNAi, extranumerary GFP-positive nuclei were consistently observed in adult worms. As NHR-25 is expressed in the anterior hyp7
daughters during postembryonic V cell divisions, we hypothesize that the loss of NHR-25 in these cells prevents their proper specification as hyp7
. Consequently these cells retain at least some features of their mothers, including expression of the seam-specific marker. (2) NHR-25 is required for proper function of the lateral hypodermis. The lateral seam of adult animals produces a cuticular structure termed alae. The prominence and continuity of these alae are markedly affected in the nhr-25
RNAi animals. The discontinuity of lateral seam is also detected using adherent junction markers. Interestingly, the most severe disruption of alae - branching - is observed after RNAi in dominant rol-6
) background. Adherent junction markers in these animals reveal the presence of extra cell boundaries which follow the pattern of the branched alae. We propose that NHR-25 is required for the proper migration of cells in the lateral hypodermis and that incorrectly assembled cuticle (as in rol-6
)) can enhance the effect of compromised hypodermal cell migration. Another possibility is that NHR-25 directly regulates expression of some cuticular components in the hypodermis and its loss thus affects the cuticular integrity. It has been shown that abnormal cuticle alone can lead to branched alae .  Asahina et al. (2000). Genes Cells 5, 711-  Gissendanner and Sluder (2000). Dev Biol 221, 259-  Eschenlauer and Page (2003). J Biol Chem 278, 4227- Supported by GAAV B5022303.