During development, progenitor cells along the rostrocaudal axis of the neural tube are instructed to become forebrain, midbrain, hindbrain or spinal cord. Cells of the caudal brain are believed to arise through reprogramming ('caudalization') of cells that initially show characteristics of rostral brain. On page 525 of this issue, Thomas Edlund and colleagues now report that Wnt signals from the posterior mesoderm are required for caudalization. FGF and retinoic acid also contribute to the induction of midbrain, hindbrain and spinal cord, but previous studies showed that these factors were not sufficient on their own. Despite earlier indications that Wnt signals were involved in specifying caudal brain character, because they have a variety of other functions in development, it was unclear whether their role in caudalization was direct or indirect. Therefore, the present work provides a crucial additional piece in this developmental puzzle.

To examine the role of Wnt signaling, the authors used explant cultures of chick neural plate along with immunohistochemical labeling for expression of a combination of transcription factors which selectivity delineate the various brain regions (yellow, rostral forebrain; red/green, rostral and caudal midbrain; light/dark blue, rostral hindbrain). When explants of caudal neural plate were taken from a stage at which the cells still exhibited primarily rostral characteristics and were co-cultured with caudal mesoderm, cells expressed markers for caudal brain regions. If Wnt signaling was inhibited, however, the cells retained their rostral character. If the authors then cultured neural plate explants from a later stage when cells were already specified to eventually make rostral, middle and caudal brain regions, they found that Wnt signaling was still directly necessary for the induction of caudal character. Finally, when explants from the eventual rostral forebrain region of the neural plate were cultured in the presence of FGF and varying concentrations of Wnt conditioned medium, the authors found that increasing concentrations of Wnt resulted in expression of progressively more caudal brain markers. Therefore, the new results firmly establish a direct role for a graded Wnt signal in directing the caudalization of neural plate cells during early neural tube development.