sucker encodes a zebrafish Endothelin-1

In all vertebrate embryos, segmental streams of cranial neural crest cells migrate to form the pharyngeal arches and differentiate into cartilages and bones of the head skeleton. In gnathostomes, the head skeleton has a dorsoventral (DV) polarity from its first appearance: dorsal and ventral cartilages of different shapes (such as the upper jaw and lower jaw in the first arch) are separated by joints. Fate-mapping studies in the avian embryo have shown that these dorsal and ventral skeletal elements arise from different anteroposterior levels of midbrain and hindbrain neural crest (Köntges and Lumsden, 1996), suggesting that before migration, the cranial neural crest is prepatterned with respect to its DV fate. Since the cranial neural crest has been shown to pattern morphogenesis of the paraxial mesodermally derived pharyngeal musculature (Noden, 1983a,b; Schilling et al., 1996), patterning information in the head periphery could be primarily contained within the premigratory neural crest. However, other experiments have established that neural crest cells are patterned by their environment after migration. For example, cartilage histogenesis of the neural crest requires contact with pharyngeal endodermal epithelium (reviewed in Hall, 1978) and chondrification of the lower jaw is inhibited by surface ectoderm (Kollar and Mina, 1991; Mina et al., 1994). Thus, pharyngeal arch development requires bidirectional signaling between the cranial neural crest and its environment. Targeted mutations in mice have revealed a signal present in the environment of the cranial neural crest which is required for ventral neural crest-derived skeletal fates. Inactivation of genes encoding either the 21-amino-acid secreted ligand Endothelin1 (Et-1), the Endothelin type A receptor (EdnrA), or the Endothelin converting enzyme (Ece-1), produces an identical craniofacial phenotype in which cartilages in the first and second arches are deleted or mispatterned (Kurihara et al., 1994; Clouthier et al., 1998; Yanagisawa et al., 1998). This common phenotype of the Et-1 and EdnrA mutant mice is remarkable given the complementary expression profiles of these genes in the arch primordia. While Et-1 is expressed in a central mesenchymal core of arch paraxial mesoderm, EdnrA is expressed in a surrounding shell of mesenchymal postmigratory neural crest cells. Et-1 is also expressed in epithelia (both surface ectoderm and pharyngeal endoderm) surrounding this entire concentric arrangement of mesenchyme (Maemura et al., 3815 Development 127, 3815-3828 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 DEV1537