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Byline: German Reig, Maria E. Cabrejos, Miguel L. Concha Keywords: Homeodomain; BarH; Barhl; FIL domains; Central nervous system; Eye; Development; Vertebrates; Drosophila Abstract: This paper reviews the developmental role of a group of homeobox-containing genes firstly described in the early nineties as critical factors regulating eye development in Drosophila. These genes received the name of BarH due to the Drosophila 'Bar' mutant phenotype and, since then, vertebrate homologues (named BarH-like or Barhl) have been described in a number of species of fish, amphibians and mammals. During embryonic development, BarH/Barhl are expressed primarily in the central nervous system where they play essential roles in decisions of cell fate, migration and survival. Transcriptional regulation mediated by these proteins involves either repression or activation mechanisms. In Drosophila, BarH is involved in morphogenesis and fate determination of the eye and external sensory organs, in regional prepatterning of the notum, and in formation and specification of distal leg segments. Vertebrate Barhl shares some functional properties with the fly counterparts, such as the ability to interact with basic helix-loop-helix (bHLH) proneural proteins, and plays crucial roles during cell type specification within the retina, acquisition of commissural neuron identity in the spinal cord, migration of cerebellar cells, and in cell survival within the neural plate, cochlea and cerebellum. Author Affiliation: Anatomy and Developmental Biology Program, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Independencia 1027, Santiago, Chile Article History: Received 5 July 2006; Revised 6 September 2006; Accepted 5 October 2006

Vertebrates have internal asymmetries along the left-right (L-R) axis revealed by organ placement about the midline. In zebrafish, Nodal signaling components are expressed asymmetrically on the left in the lateral plate mesoderm (LPM) and in the diencephalon (DI). The zebra fish gene one-eyed-pinhead (oep) is a member of the EGF-CFC family of proteins that are required cofactors for Nodal signaling. Oep embryos rescued by RNA injection for an early requirement for oep appear wild type but have defects in L-R organ placement in the viscera and the brain. Additionally, asymmetric gene expression in the LPM and DI is never established in these embryos. Similar results were obtained in zebrafish schmalspur mutants that have defects in the Nodal transducer Fast1. In both of these mutants, organs still obtain asymmetric positions, but these positions are randomized with respect to the midline. This indicates that Nodal signaling is not required for the generation of asymmetry per se, but is required to direct these asymmetries. Our analysis suggests a model where an early Nodal signaling event leads to a repression of gene expression in the LPM and DI. A later oep-dependent step is required to overcome this repression and allow for gene expression to occur. In addition, we are mapping and cloning several genes that affect L-R development in the zebra fish, and our recent results on this work will be presented.