A Systematic Survey of Expression and Function of Zebrafish <em>frizzled</em> Genes

<div><p>Wnt signaling is crucial for the regulation of numerous processes in development. Consistent with this, the gene families for both the ligands (Wnts) and receptors (Frizzleds) are very large. Surprisingly, while we have a reasonable understanding of the Wnt ligands likely to mediate specific Wnt-dependent processes, the corresponding receptors usually remain to be elucidated. Taking advantage of the zebrafish model's excellent genomic and genetic properties, we undertook a comprehensive analysis of the expression patterns of <em>frizzled</em> (<em>fzd</em>) genes in zebrafish. To explore their functions, we focused on testing their requirement in several developmental events known to be regulated by Wnt signaling, convergent extension movements of gastrulation, neural crest induction, and melanocyte specification. We found fourteen distinct <em>fzd</em> genes in the zebrafish genome. Systematic analysis of their expression patterns between 1-somite and 30 hours post-fertilization revealed complex, dynamic and overlapping expression patterns. This analysis demonstrated that only <em>fzd3a, fzd9b,</em> and <em>fzd10</em> are expressed in the dorsal neural tube at stages corresponding to the timing of melanocyte specification. Surprisingly, however, morpholino knockdown of these, alone or in combination, gave no indication of reduction of melanocytes, suggesting the important involvement of untested <em>fzds</em> or another type of Wnt receptor in this process. Likewise, we found only <em>fzd7b</em> and <em>fzd10</em> expressed at the border of the neural plate at stages appropriate for neural crest induction. However, neural crest markers were not reduced by knockdown of these receptors. Instead, these morpholino knockdown studies showed that <em>fzd7a</em> and <em>fzd7b</em> work co-operatively to regulate convergent extension movement during gastrulation. Furthermore, we show that the two <em>fzd7</em> genes function together with <em>fzd10</em> to regulate epiboly movements and mesoderm differentiation.</p>