Mammalian central nervous system neurons show asymmetry during early brain development that defines the elaborate function of neural circuitry (Kriegstein and Noctor, 2004). Many intracellular signaling pathways, which are important for the transition to the polarized state and the development of axons and dendrites, have been identified (Barnes and Polleux, 2009). How these pathways are initiated during neuronal development in vivo remained elusive until Yi et al. (2010) found that transforming growth factor-β (TGF-β) is essential for the differentiation and growth of axons. JNK is also crucial for neuronal polarity and axon formation (Oliva et al., 2006). However, whether and how JNK is activated by TGF-β signaling during brain development is not clear.

Previously, we have identified several components of the JNK pathway that play important roles during brain development (Yang et al., 2012; Xu et al., 2014). Based on these findings, we screened for MAPKKKs, the upstream kinases of the JNK pathway that are involved in neuronal development as well as TGF-β signaling. We have discovered that one of the candidates, TGF-β-activated kinase 1 (TAK1), is expressed at high level in the brain at the embryonic stage, but its expression level declines after birth (Figure 1A). Our results show that, in the neocortex of embryonic day 18.5 (E18.5) mice, TAK1 is expressed mainly in the subventricular zone, intermediate zone (IZ), and cortical plate (CP), but weakly in the ventricular zone, which is a similar expression profile to that of TGF-β receptor 2 (TβR2; Supplementary …