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First published online January 25, 2006
doi: 10.1242/10.1242/dev.02244

Development 133, 725-735 (2006)
Published by The Company of Biologists 2006
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belladonna/(lhx2) is required for neural patterning and midline axon guidance in the zebrafish forebrain

Anandita Seth1, James Culverwell1, Mitchell Walkowicz1, Sabrina Toro3, Jens M. Rick2, Stephan C. F. Neuhauss2, Zoltan M. Varga3 and Rolf O. Karlstrom1,*

1 Biology Department, University of Massachusetts, Amherst, MA 01003-9297, USA.
2 ETH Zurich and Brain Research Institute, University Zurich, Switzerland.
3 Department of Developmental Biology, University Freiburg, Freiburg, Germany.

* Corresponding author (e-mail: Karlstrom{at}bio.umass.edu)

Accepted 19 December 2005

Some of the earliest axon pathways to form in the vertebrate forebrain are established as commissural and retinal axons cross the midline of the diencephalon and telencephalon. To better understand axon guidance in the forebrain, we characterized the zebrafish belladonna (bel) mutation, which disrupts commissural and retinal axon guidance in the forebrain. Using a positional cloning strategy, we determined that the bel locus encodes zebrafish Lhx2, a lim-homeodomain transcription factor expressed in the brain, eye and fin buds. We show that bel(lhx2) function is required for patterning in the ventral forebrain and eye, and that loss of bel function leads to alterations in regulatory gene expression, perturbations in axon guidance factors, and the absence of an optic chiasm and forebrain commissures. Our analysis reveals new roles for lhx2 in midline axon guidance, forebrain patterning and eye morphogenesis.

Key words: AC, Chiasm, Commissure, Ephrin, Gfap, Glial bridge, Morpholino, Netrin, POC, Semaphorin, Slit




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