Studies of mammalian germ cell development and meiosis

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  • Recombination
  • RNAi in meiosis
  • Fanconi Anemia
  • MAPK

The Cohen lab has been instrumental in defining the role of the DNA mismatch repair (MMR) pathway in mammalian meiosis. Using mouse mutants for each of the mammalian MMR orthologs, we have determined that MSH4/MSH5 heterodimers recruit MLH1/MLiH3 to class I crossover sites in order to specify the appropriate number and spacing of crossover events in the mammalian genome.

Our continued research in this area focuses on how these crossover mediators of the class I pathway interact with mediators of the class II pathway, through recruitment and integration via key helicases and endonucleases such as BLM, EXO1, and perhaps SLX4. For more details click on image.

Small RNAs are known to be important regulators of germ cell development, primarily through the action of the germline-specific PIWI-interacting, or piRNAs. Recently, our lab has explored the role of the Argonaute family of small RNA binding proteins, focussing specifically on the class of Argonautes that are specific to microRNA and endosiRNA species, but which do not interact with the piRNAs.

Our data demonstrate that AGO4 binds microRNAs in mammalian germ cells and that this interaction is important for numerous aspects of germ cell development, particularly in meiosis. Our continued studies in this area are aimed at understanding how AGO4 and its RNA binding partners mediate essential events during prophase I and beyond in the mouse. For more details click on image.

While studying proteins that may influence meiotic crossing over in the mouse, we became interested in the newest member of the Fanconi Anemia pathway, SLX4 or FANCP. SLX4 interacts with key components of the recombinogenic machinery in mammals and, as such, is well placed to regulate cross over pathways as described elsewhere in this website.

In addition to its role in meiotic recombination, we are also investigating the role of the Fanconi network as a whole, but FANCP/SLX4 more specifically, in germ cell development. Led by Dr. Kim Holloway, these studies are aimed at understanding the role of the FA network in germ cell proliferation and genome maintenance in primordial germ cells. For more details click on image.

 

The extracellular signal regulated kinases, ERK1 and ERK2, play important roles in signaling downstream of hormones and growth factors. In ovarian cumulus cells, the ERKs are essential for mediating key events during folliculogenesis that ultimately facilitate ovulation. Studies in conjunction with the lab of Dr. Mark Roberson are ongoing to explore the role of the ERKs in meiotic prophase I and in events specifically within the oocyte of the adult ovary. For more details click on image.

 

in the news ....

*** NEW PAPER: see our recent publications !!

Congratulations Dr. Mohan !!!

Congratulations to Swapna Mohan for successfully defending her thesis! Swapna has now left the cold weather of Ithaca behind her and is basking in the sunshine of Texas. We wish her all the best of luck in the next phase of her career.

Goodbye to Andrew and Swapna !!

The lab is very sad to say farewell to Dr. Andrew Modzelewski, who has moved to Berkeley to take up a postdoctoral research position in the lab of Dr. Lin He. We wish him the best of luck in this new adventure!

Also, farewell to Dr. Swapna Mohan, who has moved to Texas and is currently deciding on her next career move. We will miss her and all her oocyte knowledge! Best of luck, Swapna!

 

The role of HEI10 in directing class I crossovers in the mouse

We are proud to have played a part in a new publication from our friend and collaborator, Dr. Neil Hunter. In this paper, Neil's lab, together with the lab of John Schimenti, demonstrate a critical role for HEI10 in modulating DSB repair events towards crossover designation. See our publications page for further details.