, 2009). Given recent evidence that radially aligned cells arising from a common progenitor have a high probability of interconnecting ( Yu et al., 2009), the tangential dispersion at the multipolar cell phase may also be critical for establishing intercolumnar cortical connectivity ( Costa and Hedin-Pereira, 2010). Our work adds

to these findings by demonstrating that the timing and Volasertib duration of the multipolar phase is precisely regulated by FoxG1 activity. Pulse-chase studies have shown that cell birth date within the cortex predicts laminar position (Angevine and Sidman, 1961 and Rakic, 1974). A now classic transplantation study found that cell fate could be altered depending on whether pyramidal neurons underwent their last neuronal division in an isochronic or heterochronic host environment (McConnell and Kaznowski, 1991). Our study adds to this finding by demonstrating that the laminar position and postnatal marker expression of pyramidal neurons remains labile at least up to the early multipolar phase. In this regard, both the laminar (Kwan et al., 2008 and Lai et al., 2008) and

areal (Joshi et al., 2008) identity of pyramidal neurons require the persistent expression of the transcription factors (Sox5 and BhlhB5), which are exclusively restricted to postmitotic cells. It will take further analysis to establish whether the mispositioning of pyramidal neurons upon FoxG1 gain-of-function results in changes in their hodological identity. Nonetheless, it is becoming evident that rather than being irreversibly fixed, pyramidal neurons require active maintenance in their identity, Palbociclib molecular weight demonstrating that the line between developmental programs and adult plasticity is less absolute than previously recognized. In addition to its roles in axon outgrowth and growth cone turning in commissural projection neurons (Serafini et al., 1994), Netrin-signaling has been shown to mediate both attraction and repulsion during cell migration (Ackerman et al., 1997, Alcántara et al., 2000, Hu and Rutishauser, 1996, Stanco et al., 2009 and Xu et al.,

2010). below It has also been suggested that Netrin-signaling controls axon outgrowth and cell migration through distinct downstream mechanisms (Causeret et al., 2004). Here, we show that, in the case of pyramidal neuron precursor migration, Unc5D and Dcc function in concert during the multipolar cell phase. In this context, FoxG1 appears to regulate the expression of Unc5D but not Dcc. Interestingly, in Drosophila motorneurons akin to the present context, Unc5 is positively regulated by the transcription factor Even-skipped, whereas Frazzled (the fly homolog of Dcc) is not ( Labrador et al., 2005). Netrins and, more recently, Flrts (Fibronectin type III domain and leucine-rich repeats transmembrane protein) have been demonstrated to interact with Unc5 receptors (Karaulanov et al., 2009 and Yamagishi et al., 2011).