Left: the neural plate of a zebrafish embryo. Dark staining indicates the telencephalic territory. Right: brain of a three-day-old zebrafish stained with an antibody to show axonal pathways in the telencephalon (T), eyes (E) and hypothalamus (H). Courtesy of Corinne Houart, MRC Centre for Developmental Neurobiology, King's College London, UK.

The telencephalon is the most anterior structure to arise from the neural tube, and its development — from a simple neuroepithelium to a highly complex structure consisting of cerebral cortex and basal ganglia — has been the subject of many studies. However, an even more fundamental question still remains to be answered: how is the telencephalon induced in the first place? In a new paper in Neuron, Houart et al. provide us with some answers.

In the zebrafish, induction of the telencephalon requires signals from the anterior boundary of the neural plate (ANB). If this tissue is ablated, telencephalon-specific genetic markers fail to be activated. Conversely, transplanting the ANB to more posterior regions of the neural tube causes upregulation of telencephalic markers.

The authors identified a new gene called tlc, which encodes an antagonist of the Wnt signalling pathway and is expressed in the ANB at the time of telencephalic induction. They found that Tlc-expressing cells could restore telencephalic gene expression after ablation of the ANB, and that these cells could also activate these genes in more posterior regions. By contrast, overexpression of Wnt proteins inhibited telencephalic cell fates.

These results indicate that Wnt antagonism is required for induction of the telencephalon, and that Tlc can act as the antagonist. But is Tlc actually the endogenous signal that initiates telencephalic development in the zebrafish? To test this, Houart et al. inactivated Tlc in wild-type embryos using an antisense oligonucleotide. They found that, like ablation of the ANB, this manipulation led to a loss of early telencephalic marker-gene expression, making Tlc a strong candidate for being an important component of this endogenous signal.

The next step will be to find out whether Tlc has functional homologues in other vertebrate species. Although it is similar in sequence to members of the mammalian sFRP family of Wnt antagonists, none of these has yet been shown to be expressed in the mammalian equivalent of the ANB. However, mutations in other Wnt antagonists, such as the mouse dickkopf gene, can cause loss of telencephalic structures. Taken together with the latest discovery, this indicates that studying the role of Wnt antagonism puts us on track for elucidating the molecular basis of telencephalic induction.