Gaurav Sharma ’22

Invasion through the basement membrane is essential to many cellular and biological processes such as embryonic development, immune response, tissue development, and metastasis. The components and mechanism of basement membrane invasion is known. There are four transcription factors that regulate anchor-cell invasion; fos-1, hlh-2, nhr-67, and egl-43. The Matus Lab at Stony Brook University sought to answer the question of how all these transcription factors regulate each other and interact with each other. 

The Matus Lab used C. elegans to study basement membrane invasion because the uterine-vulval connection is generated by the anchor-cell (specialized uterine cell) invading through the basement membrane of the epithelium cell of the vulva.  Transcription factors were tagged using CRISPR/Cas9 and RNA interference plates were used to knock down the gene for the specific transcription factor. It was found that having losing egl-43 and hlh-2 resulted in multiple anchor-cells being present which may be due to the loss of cell cycle arrest and nhr-67 activity. egl-43 was detected to auto-regulate itself and it was seen that egl-43 and hlh-2 regulate nhr-67 in a feed forward loop. It’s also important to note that these transcription factors were found to be active after specification of the anchor-cell. The expression timeline went from expression of egl-43 only followed by  hlh-2, nhr-67, and then fos-1. The relative concentrations of each transcription factor increased during just prior and during invasion.   

These findings present a relationship among transcription factors that may be present in mammalian cells. Other researchers can use these findings and methodology to see if mammalian cell basement membrane invasion also has the same mechanisms as that of C. elegans. Metastasis can also be targeted by controlling the transcription factors that cause invasion through the basement membrane to occur. Currently, the Matus Lab is looking into more about cell cycle fate concerning anchor cell invasion as well as cellular indications that decides which cell becomes the anchor cell and which becomes the ventral uterine cell. 

[1] Medwig-Kinney et al. A developmental gene regulatory network for C. elegans anchor cell invasion. Development. 147, (2020). doi:10.1242/dev.185850

[2] Image retrieved from: https://www.stonybrook.edu/commcms/biochem/research/faculty/matus/#ResearchDescription