The vertebrate brain develops from a bilaterally symmetric neural tube but later displays profound anatomical and functional asymmetries. Despite considerable progress in deciphering mechanisms of visceral organ laterality, the genetic pathways

It has long been argued that hemispheric specialization of brain functions, such as language or handedness, correlates with anatomical asymmetries between the left and right sides of the brain (refer to Galaburda et al., 1978; Witelson and Kigar, 1988). Prominent left-right (L-R) structural differences have been described for the human brain, notably the length and slope of the Sylvan fissure and the size of the planum temporale (Geschwind and Levitsky, 1968; Galaburda et al., 1978; LeMay, 1982). Anatomical asymmetries have also been noted in the brains of lower vertebrates, particularly in the diencephalic region of the forebrain (Harris et al., 1996; Braitenberg and Kemali, 1970). However, there is little information as to how differences between the left and right sides of the brain arise in any species or what mechanisms regulate asymmetric brain development. In contrast, considerable progress has been made in deciphering the genetic pathways that underlie asymmetry of the viscera. The visceral organs of vertebrates have characteristic left-right asymmetries in their placement and morphology, such as the rightward looping of the embryonic heart tube and its left-sided position (Fishman and Chien, 1997; Capdevila et al., 2000; Schier and Shen, 2000). Although there are some differences in how laterality of the viscera is achieved, many of the mechanisms and signaling pathways regulating development of the L-R axis are shared between species. A highly conserved feature is asymmetric expression in the left lateral plate mesoderm (LPM) of genes encoding the TGFβ-related signal Nodal (Levin et al., 1995; Collignon et al., 1996; Lowe et al., 1996; Lustig et al., 1996; Sampath et al., 1997), the Lefty/Antivin antagonists of Nodal signaling (Meno et al., 1996, 1997, 1999; Kosaki et al., 1999; RodriguezEsteban et al., 1999; Ishimaru et al., 2000; Cheng et al., 2000; Thisse et al., 2000) and Pitx2, a downstream transcriptional effector of Nodal action (Logan et al., 1998; Piedra et al., 1998; Ryan et al., 1998; St Amand et al., 1998; Yoshioka et al., 1998; Campione et al., 1999; Gage et al., 1999; Kitamura et al., 1999; Lin et al., 1999; Lu et al., 1999; Patel et al., 1999; Schweickert et al., 2000). This signaling cassette influences the morphology of the heart and other visceral organs (refer to Capdevila et al., 2000; Schier and Shen, 2000). In the zebrafish ( Danio rerio), the nodal-related genes quint (sqt) and cyclops(cyc) are expressed at gastrulation, when they mediate development of mesoderm, endoderm and ventral neurectoderm (Sampath et al., 1998; Rebagliati et al., 1998a,b; Erter et al., 1998; Feldman et al., 1998), and require the membrane-associated protein One-eyed pinhead (Oep) to effect their signaling (Gritsman et al., 1999) . The cyc gene is expressed again during somitogenesis, in the left LPM and left 5101 Development 127, 5101-5112 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 DEV5406