The tailless family of nuclear receptors is highly conserved among animals. In humans, it functions in regulating neuronal stem cell differentiation. The C. elegans tailless ortholog, nhr-67, is expressed in a dynamic pattern in pre-uterine cells: initially in the 4 pre-VU cells during the L2, then upregulated in the anchor cell (AC) in response to the lin-12/lag-2 Notch reciprocal signaling system. During the L3 stage, nhr-67 expression is maintained at high levels in the AC and at low levels in VU descendants that produce the adult ventral uterus. nhr-67 is required for expression of the lin-12/Notch receptor in pre-VU and VU cells and for multiple markers of AC identity, indicating that it functions in differentiation of both uterine cell types.
Deletion of a 276bp region of the nhr-67 promoter results in a loss of nhr-67 expression in pre-VU, AC, and VU cells. Expression of 276bp region::gfp shows the region is necessary and sufficient for nhr-67 expression during ventral uterine development. The region includes two E box sequences that we propose bind the HLH-2 transcription factor, which functions in AC and pre-VU development. We have performed site-directed mutagenesis to delete the E boxes and four other conserved elements from the 276bp promoter region and tested their functions directly in vivo. Our data demonstrate the primary role of the E box sequences in regulating nhr-67 in the AC, pre-VU, and VU cells. Funded by the NIGMS..