Role of BMP signaling and the homeoprotein iroquois in the specification of the cranial placodal field

Abstract

Different types of placodes originate at the anterior border of the neural plate but it is still an unresolved question whether individual placodes arise as distinct ectodermal specializations in situ or whether all or a subset of the placodes originate from a common preplacodal field. We have analyzed the expression and function of the homeoprotein Iro1 in Xenopus and zebrafish embryos, and we have compared its expression with several preplacodal and placodal markers. Our results indicate that the iro1 genes are expressed in the preplacodal region, being one of the earliest markers for this area. We show that an interaction between the neural plate and the epidermis is able to induce the expression of several preplacodal markers, including Xiro1, by a similar mechanism to that previously shown for neural crest induction. In addition, we analyzed the role of BMP in the specification of the preplacodal field by studying the expression of the preplacodal markers Six1, Xiro1, and several specific placodal markers. We experimentally modified the level of BMP activity by three different methods. First, we implanted beads soaked with noggin in early neurula stage Xenopus embryos; second, we injected the mRNA that encodes a dominant negative of the BMP receptor into Xenopus and zebrafish embryos; and third, we grafted cells expressing chordin into zebrafish embryos. The results obtained using all three methods show that a reduction in the level of BMP activity leads to an expansion of the preplacodal and placodal region similar to what has been described for neural crest regions. By using conditional constructs of Xiro1, we performed gain and loss of function experiments. We show that Xiro1 play an important role in the specification of both the preplacodal field as well as individual placodes. We have also used inducible dominant negative and activator constructs of Notch signaling components to analyze the role of these factors on placodal development. Our results indicate that the a precise level of BMP activity is required to induce the neural plate border, including placodes and neural crest cells, that in this border the iro1 gene is activated, and that this activation is required for the specification of the placodes.

Evolution of the neural crest viewed from a gene regulatory perspective

“…A moderate-throughput transcriptome analysis reveals that the expression patterns of signaling molecules and neural plate border specifiers appear to be highly conserved in lamprey, as do the functions of the border specifiers tested (SaukaSpengler et al, 2007). For example, BMP, Wnt, and Delta expression patterns are similar to those noted in jawed vertebrates (Endo et al, 2002;Garcia-Castro et al, 2002;Glavic et al, 2004a;Glavic et al, 2004b;Hollyday et al, 1995;LaBonne and Bronner-Fraser, 1998;Mayor and Aybar, 2001;Nguyen et al, 1998;Roelink and Nusse, 1991;Saint-Jeannet et al, 1997;Sasai and De Robertis, 1997). Thus, signaling cues are present in lamprey at a proper time and place to play an analogous function in neural crest specification as in other vertebrates.…”

The preplacodal region: an ectodermal domain with multipotential progenitors that contribute to sense organs and cranial sensory ganglia

“…In support of this idea, Xenopus animal caps treated with different concentrations of BMP antagonists form epidermis in the presence of high levels of BMP activity, while neural crest and preplacodal cells are generated at intermediate and neural plate at low levels (Wilson, et al, 1997;Tribulo, et al, 2003;Brugmann, et al, 2004;Glavic, et al, 2004). Likewise, zebrafish mutants with reduced BMP activity (and thus a shallower gradient) show a relatively larger expansion of the neural crest territory than of the neural plate (Nguyen, et al, 1998;Barth, et al, 1999).…”

“…In contrast, modulation of the BMP pathway away from the border does not have any effect. Likewise, local reduction of BMP signalling close to the preplacodal region expands this territory in chick and Xenopus, but is not sufficient to induce it ectopically in future epidermis (Glavic, et al, 2004;Ahrens and Schlosser, 2005;Litsiou, et al, 2005). One possible explanation to reconcile these differences is that Xenopus animal caps may contain border territory and are therefore particularly sensitive to changes in BMP activity.…”

“…Mice deficient in Gbx2 (Lin, et al, 2005) and Pax2 function show patterning defects in the otic vesicle (Torres, et al, 1996;Burton, et al, 2004), while loss of Six3 or Pax6 affects lens and olfactory development (Hogan, et al, 1988;Quinn, et al, 1996;Grindley, et al, 1997;Lagutin, et al, 2003;Liu, et al, 2006). In Xenopus, Irx1 is required for the expression of the early preplacodal marker Six1 and later placode specific genes like Sox2 and Pax2 (Glavic, et al, 2004). Thus, mutation in or loss of any of these genes leads to defects in placode development, although their role in early patterning of the preplacodal region remains elusive probably due to functional redundancy with other members of the same family that are expressed in similar patterns (Schlosser, 2006).…”

Ras-dva, a member of novel family of small GTPases, is required for the anterior ectoderm patterning in theXenopus laevisembryo

“…The FGF signaling pathway is known to cooperate with that of BMP and Wnt during regulation of the early development of the neural crest (Deardorff et al, 2001;McGrew et al, 1997;Glavic et al, 2004;Streit and Stern, 1999). In particular, an intermediate level of BMP signaling at the lateral borders of the neural plate is crucial for neural crest induction (Aybar and Mayor, 2002), and this intermediate level is achieved through phosphorylation by the FGF signaling pathway of the BMP effector Smad1 (Pera et al, 2003).…”