Functional roles of rx3 and Shh in the hypothalamus of the zebrafish.

The rx/Rax gene is a conserved homeobox transcription factor that is known to
play an important role in the development of the eye. Mutations in rx/Rax gene
manifest in the congenital loss of eyes known as anophthlamia or the development
of small-eyes; microphthlamia. Despite numerous literatures describing the
expression of Rx/Rax in the anterior hypothalamus of several model organisms, its
function there is still hugely unknown and remains to be investigated. In order to
gain insight into the role of rx, I have performed experiments aimed at
understanding the signalling events governing the expression and function of rx3, a
homologue of rx/Rax, in the anterior hypothalamus of the embryonic zebrafish
model system.
Several studies have shown the reduction of pomc expressing neurons in the
arcuate nucleus ofthe hypothalamus when the function of rx3/Rax is
compromised. Here I have shown that rx3 may, together with the signalling
molecule sonic hedgehog (Shh), act to specify and promote the differentiation of
progenitor cells to the Pomc cell fate. The functional loss of either rx3 or Shh leads
to a decrease in the number of pomc expressing neurons in the arcuate nucleus;
located adjacent to the rx3 and shh expressing domains at the anterior
hypothalamus. Further analyses reveal that rx3 and Shh may mutually activate
each other's expression during the early establishment of the anterior dorsal
hypothalamus. Experiments also show that Fgf may operate upstream of rx3 to
regulate its expression; as well as the number of pomc positive cells in the arcuate
nucleus. These studies show for the first time, a role for rx3 in the development of
the anterior hypothalamus and the differentiation of pomc positive progenitors in
the arcuate nucleus through its interaction with Shh.
Additionally, I have found the signalling factors Shh and Fgf3 to be maintained in
the adult zebrafish hypothalamus. Furthermore, I have evidence to suggest a role
for Shh in governing the proliferation of neural progenitor cells in the medial
hypothalamus of the adult zebrafish. This study is the first to investigate neural
stem/progenitor cells in the hypothalamus of the adult zebrafish.