Meeting Abstract
The MEN1 gene is an important regulator of patterning and cell growth during vertebrate embryogenesis. Mutations in human MEN1 cause tumors of the parathyroid, pancreas and anterior pituitary. The MEN1 gene encodes a protein that acts as a cofactor of the MLL protein, and together these proteins activate the expression of critical developmental genes and cell-cycle regulators including the homeobox transcription factors HoxA9 and Meis, as well as the cyclin-dependent kinase inhibitor p27. The Nematostella vectensis (Anthozoa, Cnidaria) genome encodes a single highly conserved ortholog of MEN1 (NvMEN1). The crystal structure for NvMen1 has been solved and shown to bind NvMLL. In an effort to develop N. vectensis as a model system for understanding the MEN1 gene regulatory network we have characterized the embryonic expression of NvMen1, NvMLL, Nvp27, NvMeis, and the Hox gene NvAx1a by whole-mount in-situ hybridization. We show that these five genes are expressed in partially overlapping spatial and temporal domains. Our data suggest that NvMen1 might share the same co-factors and targets as the vertebrate MEN1 gene. To functionally characterize NvMen1, we have used CRISPR/Cas9 genome editing to delete the gene from the N. vectensis genome. From this knockout we show phenotypic evidence consistent with a role of MEN1 in development and cell cycle. We also show the effects NvMEN1 knockouts on NvMLL, Nvp27, NvMeis, and NvAx1a. Our data show that N. vectensis is an up-and-coming model for studying MEN1 and has the potential for overcoming some of the technical difficulties that have hampered the study of this gene in traditional model systems.
