Rx3 and Shh direct anisotropic growth and specification in the zebrafish tuberal/anterior hypothalamus.

In the developing brain, growth and differentiation are intimately linked. Here we show that in the zebrafish embryo, the homeodomain transcription factor rx3 co-ordinates these processes to build the tuberal/anterior hypothalamus. Analysis of rx3 chk mutant/rx3 morphant fish and EdU pulse-chase studies reveal that rx3 is required to select tuberal/anterior hypothalamic progenitors and to orchestrate their anisotropic growth. In the absence of rx3 function, progenitors accumulate in the 3(rd) ventricular wall, die or are inappropriately-specified, the shh+ anterior recess does not form, and its resident pomc+, ff1b+ and otp+ TH+ cells fail to differentiate. Manipulation of Shh signalling shows that shh co-ordinates progenitor cell selection and behaviour by acting as an on-off switch for rx3 Together our studies show that shh and rx3 govern formation of a distinct progenitor domain that elaborates pattern through its anisotropic growth and differentiation.