Function of the Eph-related kinase rtk1 in patterning of the zebrafish forebrain

Abstract

Early during its development, the vertebrate brain is subdivided into regions that have distinct fates and correlate with the expression domains of regulatory genes, but little is known about the cell-cell interactions that establish this spatial pattern. Candidates for regulating such interactions are the Eph-related receptor tyrosine kinases (RTKs) which have spatially restricted expression in the developing brain. These RTKs may mediate cell-contact-dependent signalling by interacting with membrane-bound ligands, and have been implicated in axon repulsion and the segmental restriction of gene expression in the hindbrain, but nothing is known regarding their function in the rostral neural epithelium. Here we use a dominant-negative approach in the zebrafish embryo to interfere with the function of Rtk1, an Eph-related RTK expressed in the developing diencephalon. We find that expression of a truncated receptor leads to expansion of the eye field into diencephalic territory and loss of diencephalic structures, indicating a role for Rtk1 in patterning the developing forebrain.

Identification of Elf-1 and B61 as high affinity ligands for the receptor tyrosine kinase MDK1

“…Whereas MDK1 shows high expression in the rostral part (Ciossek et al, 1995;Ellis et al, 1995), Elf-1 transcripts are detected in the caudal region of the hindbrain (Cheng and Flanagan, 1994 and data not shown). Since the expression of a truncated Sek receptor tyrosine kinase disrupts the segmental restriction of gene expression during early rhombomere speci®cation, Sek has been suggested to be involved in the interactions that regulate the segmental identity or movement of cell leading to a sorting of cell with odd and even segmental identity (Xu et al, 1995). It is tempting to speculate that due to their contrasting expression MDK1 and Elf-1 might be involved in early patterning events during midbrain development.…”

“…Several RTKs of this family have restricted expression domains in di erent rhombomeres (Becker et al, 1994). Especially Sek (Gilardi-Hebenstreit et al, 1992) seems to be playing a role in segmental restriction of gene expression in the odd-numbered rhombomeres r3 and r5 (Xu et al, 1995) as well as in patterning of the zebra®sh forebrain (Xu et al, 1996). In addition, expression of Cek-8, the chicken homologue of Sek, has been reported to respond to regulatory signals during limb patterning (Patel et al, 1996).…”

Ephrin-B3, a ligand for the receptor EphB3, expressed at the midline of the developing neural tube

“…Axon guidance functions have also been implicated by studies of other developmental systems, including topographic mapping of the hippocamposeptal projection, establishment of tracts across the midline of the brain, and guidance of developing sensory and motor spinal nerves (Donoghue et al, 1996;Gao et al, 1996;Henkemeyer et al, 1996;Kilpatrick et al, 1996;Ohta et al, 1996;Orioli et al, 1996;Zhang et al, 1996;Park et al, 1997;Wang and Anderson, 1997). The ephrins have also been implicated in the establishment of regional pattern in the nervous system, including the control of neural crest migration, the establishment of rhombomere boundaries in the hindbrain, and the organization of the diencephalon (Krull et al, 1997;Smith et al, 1997;Xu et al, 1995Xu et al, , 1996.…”

Identification of XLerk, an Eph family ligand regulated during mesoderm induction and neurogenesis in Xenopus laevis

“…Pagliaccio (XSek-1) is expressed in the marginal zone and neural crest cells during development (Winning and Sargent, 1994). Ectopic expression of dominant negative XSek-1 (Pag) during Xenopus development disrupts segmental restriction from rhombomeres three to ®ve (Xu et al, 1995). Moreover, expression of an EGF (extracellular domain)/ Pagliaccio (intracellular kinase domain) chimera during early embryogenesis caused embryonic blastomeres to disaggregate by the late blastula stage, implicating a role for this receptor in cell adhesion or cell motility (Winning et al, 1996).…”