, 2007 and Khodosevich MG-132 et al., 2009). While the role of CTGF in wound healing and fibrosis is established, little is

known about its role under normal physiological conditions (Shi-Wen et al., 2008). In the OB, CTGF is detected in the glomerular layer at postnatal day 3 (P3), peaks at P5, and continues to be expressed in into adulthood (Khodosevich et al., 2013). This coincides with a time of rapid cellular and anatomical expansion of the sensory epithelium. The CTGF-positive cells coexpress cholecystokinin (CCK) and are glutamatergic, characteristic of external tufted cells (Liu and Shipley, 1994 and Ohmomo et al., 2009). Although CTGF was detected primarily postnatally, the external tufted cells are primarily born embryonically during bulb development. Consistent with their identification as external tufted cells, CTGF-positive neurons were generated during the peak of OB development (E16–18), and their birth completed by P0. Together these observations suggest that earlier-born external tufted cells adopt a new and selective role that involves CTGF in the postnatal and adult animal. Rather than depend on tissue-specific conditional knockouts, the authors utilized adeno-associated virus (AAV) that robustly

infects all cell types—dividing and nondividing in the OB. Their experiments have revealed an interesting intercellular control mechanism Ferroptosis inhibitor that modulates the number of inhibitory interneurons. The authors combined expression manipulations that decreased CTGF expression with retroviral EGFP reporter-marking of SVZ neuroblasts at P3 and observed an increase in the number of EGFP-positive cells in the glomerular layer. This effect was reversed when a shRNA-resistant form of CTGF was injected. Morphological analysis identified EGFP-positive cells in the glomerular layer as periglomerular neurons. Why were more periglomerular cells present in the CTGF knockdown brains? During the first few weeks

after the newborn neurons reach the OB, roughly half of them undergo apoptosis. The authors hypothesized that knockdown of CTGF selectively altered apoptosis of periglomerular Terminal deoxynucleotidyl transferase but not granule cells. The number of apoptotic cells in the glomerular layer but not the granule cell layer decreased in the CTGF knockdown mice. Injecting shRNA-resistant CTGF increased the number of apoptotic cells. Thus, CTGF seemed to play a role in promoting apoptosis of periglomerular cells. Although the role of CTGF in inhibitory interneuron survival was clear, the signaling pathway that mediated the effects of the tufted cell-derived factor was more enigmatic. In particular, the receptors for canonical CTGF signaling are not expressed in the maturing neuroblasts of the olfactory bulb. CTGF is also known to bind to other growth factors and modulate their activity (Cicha and Goppelt-Struebe, 2009).