lithium-chloride and Eye-Abnormalities

Wnts have been shown to provide a posteriorizing signal that has to be repressed in the specification of vertebrate forebrain region. Previous studies have shown that Wnt activation by LiCl treatment causes an expansion of optic stalk and mid-hindbrain boundary, whereas eye and ventral diencephalon in the forebrain region were reduced. However, the molecular mechanism, by which inhibits Wnt activity in the forebrain remains poorly defined. To investigate relationship between forebrain specification and Wnt signaling, the zebrafish homologue of secreted frizzled related protein1 (sfrp1) has been characterized. The transcripts of sfrp1 are detected in the presumptive forebrain at gastrula and in the ventral telencephalon, ventral diencephalon, midbrain and optic vesicles at 24h after postfertilization (hpf). Overexpression of sfrp1 causes an anteriorization of embryo, with enlarged head and reduced posterior structure as in the embryo overexpressing dominant-negative form of Frizzled8a or Dkk1. Its overexpression restored the eye defects in the Wnt8b-overexpressing embryos, but not in the LiCl-treated embryos. These results suggest that Sfrp1 expressed in the forebrain and eye field plays a critical role in the extracellular events of antagonizing Wnt activity for the forebrain specification.

Topics: Animals; Body Patterning; Cytoskeletal Proteins; Eye; Eye Abnormalities; Gastrula; Gene Expression Regulation, Developmental; Intercellular Signaling Peptides and Proteins; Lithium Chloride; Mesencephalon; Nervous System Malformations; Organogenesis; PAX2 Transcription Factor; Prosencephalon; Signal Transduction; Visual Pathways; Wnt Proteins; Zebrafish; Zebrafish Proteins

Ocular malformations such as synophthalmia and cyclopia occur in all vertebrates including humans. We induced fused eye anlagen by exposure of Xenopus laevis embryos to dissolved LiCl. Three basic forms of malformations were observed in the rostral CNS; these represent major steps in a continuous sequence of ocular abnormalities: (i) "hour-glass eyes", (ii) synophthalmia, and (iii) cyclopia vera. The type of abnormity induced seemed to depend on the time and/or the dosage of LiCl exposure. In all cases studied, the histology of the retinae was normal. We reconstructed olfactory organs, eyes, and rostral portions of the CNS from serial sections of 16 Xenopus larvae. Our results confirm that defective bilateralization affects all parts of the rostral CNS and suggest that the telencephalon displays the weakest, and the eyes have the highest, resistance against midline fusion. Defective bilateralization also involves the pineal anlagen, as duplication or enlargement of the pineal organs occurred in most cases with ocular fusion. We conclude that LiCl-induced interferences with ontogenetic bilateralization of prosencephalic structures are the consequence of an elimination of an, as yet, undefined bilateralization signal from (ventral) midline structures of the neural plate and tube.

Topics: Abnormalities, Drug-Induced; Animals; Brain; Central Nervous System; Embryo, Nonmammalian; Eye Abnormalities; Humans; Lithium Chloride; Vertebrates; Xenopus laevis