SOX and stem cells Lovell-Badge lab

057: SOX and stem cells Lovell-Badge lab

Created by Karine Rizzoti and Robin Lovell-Badge

Coincident with the cloning of Sry, the mammalian Y-linked testis determining gene, we isolated the first few members of what we termed the Sox gene family, of which there are 20 in mouse and humans. Their protein products are related through the possession of an SRY-like HMG Box DNA binding domain. Subsequent structural and molecular studies, by us, our collaborators and by others, revealed that the HMG domain actually has a sock-like shape. When it binds DNA it intercalates into the minor groove causing the DNA to bend through an angle of about 90o. The non-HMG box parts of the SOX proteins can include activation and/or repression domains. It is therefore thought that they function both to help organize or stabilize chromatin architecture as well as directly contributing to the control of target gene transcription.

Several of the Sox genes we chose to work on, notably Sox2 and Sox9, have pleiotropic roles during development and in stem cells in the adult. For example, we showed that SOX2 is essential for pluripotent cells in the early embryo, such as those of the early epiblast and inner cell mass of the blastocyst (top left), embryonic and other pluripotent stem cells in culture (bottom left), progenitors in the developing hypothalamo-pituitary axis (top right), and neural stem cells (NSCs) in vitro and in vivo, including in specialised niches in the adult brain (bottom right). In the embryo, maintenance of early pituitary progenitors (top left, blue) depends on signals from the overlying ventral diencephalon (green). In the adult brain NSC niche (bottom right), in the lateral ventricles, ependymal cells (green), and the microvasculature (red) contribute signals that help to regulate activation, proliferation and differentiation of the NSCs.

Pearls, sequins, petri dish (pierced with a warm needle), stuffed sock and mouse were sewn on the painted canvas.

057-SOX and stem cells Lovell-Badge lab