prdm1 (PR domain containing 1, with ZNF domain) or Blimp-1 (B lymphocyte-induced maturation protein 1) is a zinc-finger-containing transcriptional regulator that plays critical developmental roles in a wide range of species including insects, worms, echinoderms, and all vertebrates (Bikoff et al., 2009; John and Garrett-Sinha, 2009). Several studies have demonstrated that prdm1 acts by recruiting a range of epigenetic histone modifiers (histone methylases and deacetylases) in a sequence-specific manner (Yu et al., 2000; Gyory et al., 2004; Ancelin et al., 2006; Su et al., 2009). prdm1 plays important roles in cell fate decisions, by repressing large sets of genes and dramatically altering a cell's transcriptional profile. Loss-of-function prdm1 mutants and morphants exhibit complete loss of the cell type in which the gene is expressed, further underscoring the developmental importance of this gene (Roy and Ng, 2004; Vincent et al., 2005; Wilm and Solnica-Krezel, 2005; Robertson et al., 2007; Brzezinski et al., 2010).
The neural crest is a vertebrate-specific multipotent migratory embryonic cell population, which forms most of the peripheral nervous system, cranium, and pigment cells. Much progress has been made in the recent years in understanding genetic mechanisms underlying neural crest formation, and this information has been assembled into a proposed neural crest gene regulatory network (Sauka-Spengler and Bronner-Fraser, 2008; Betancur et al., 2010). Extensive analysis of the neural crest gene regulatory network in the lamprey, the most basal extant vertebrate, demonstrated that there is a great deal of conservation in the genetic mechanisms responsible for neural crest formation to the base of vertebrate lineage, particularly at early stages (Sauka-Spengler et al., 2007).
Data from several zebrafish mutants show that prdm1 is essential for the specification of the common progenitor of the neural crest and Rohon-Beard (RB) sensory neurons. Two prdm1 fish mutants, narrowminded and U-boot, exhibit a decrease in the number of neural crest cells, and all neural crest derived structures are much smaller than in the wild-type fish (Artinger et al., 1999; Roy and Ng, 2004; Hernandez-Lagunas et al., 2005). The null prdm1 mutant, narrowminded, also exhibits a complete loss of RB neurons (Hernandez-Lagunas et al., 2005). Interestingly, however, there are no reports on a similar function for prdm1 or any other member of the prdm family in other species. prdm1 is not expressed in the neural plate border or neural crest of mouse embryos, and no defects in the early steps of neural crest formation are seen in any prdm1 mouse knockouts (Chang et al., 2002; Vincent et al., 2005; Robertson et al., 2007). It is possible, however, that prdm1 is expressed and functions in the neural crest component of the branchial arches in the mouse at later stages. Expression of prdm1 is seen at E10.5 in the mesenchyme of the mouse branchial arches (Chang et al., 2002; Robertson et al., 2007). prdm1-null mice exhibit a complete loss of all branchial arches posterior to the first arch, which could be due to a cell-autonomous neural crest defect or to a failure of the neural crest migration (Vincent et al., 2005; Robertson et al., 2007). No expression of prdm1 in neural crest of chick and lamprey embryos has been reported; however, it is possible that the embryonic stages examined were too late to detect it (Ha and Riddle, 2003; Hammond et al., 2009). It is not clear at present whether prdm1's role in zebrafish neural crest is specific to the fish lineage, or if this gene has an ancestral role in the neural crest development that had been lost in the mouse. To address this question, we isolated a full-length sequence for prdm1 from an embryonic cDNA library of the sea lamprey Petromyzon marinus, and examined prdm1 expression pattern at a range of embryonic stages. We found strong expression of this gene in the lamprey neural plate border and premigratory neural crest, suggesting an ancestral role in neural crest development. We next investigated prdm1 loss-of-function phenotype and found that it plays a role in the specification of the mesoderm, which precedes and masks any possible function in the neural plate border. Finally, we examined the upstream inputs into prdm1 in the neural plate border, and found that Msx A and AP-2 function as upstream activators of prdm1 transcription.