Ptn–Brd2 antagonism in neurons

Bromodomain-containing protein 2 (Brd2) is an essential cell cycle regulator and is widely expressed during development; paradoxically, however, it can also be detected in differentiating neurons. Previous investigations into new Brd2 partners by the authors identified the growth factor pleiotrophin (Ptn). Ptn acts as an antagonist of the cell-cycle-stimulating activity of Brd2, enhancing neuronal differentiation, and Ptn knockdown reduces neuronal differentiation. Here, Mario Garcia-Dominguez and colleagues (p. 2554) analyse the interaction between Ptn and Brd2 during neuronal differentiation. The authors show that Ptn stimulates neuronal differentiation by antagonising Brd2, demonstrating that this antagonism occurs in a cell differentiation model, and in spinal cord neurogenesis and neural crest migration. Moreover, they explored the mechanisms by which Ptn interferes with Brd2 function, finding that Ptn destabilises the association of Brd2 with chromatin. These data suggest that Ptn enhances induced neuronal differentiation by antagonising the cell-cycle-stimulating activity of Brd2. The authors therefore propose that the interaction between Ptn and Brd2 is involved in modulating the balance between proliferation and differentiation during vertebrate neurogenesis.