Off-campus UMass Amherst users: To download dissertations, please use the following link to log into our proxy server with your UMass Amherst user name and password.

Non-UMass Amherst users, please click the view more button below to purchase a copy of this dissertation from Proquest.

(Some titles may also be available free of charge in our Open Access Dissertation Collection, so please check there first.)

Cloning and functional characterization of the zebrafish mutation belladonna

Anandita Seth, University of Massachusetts Amherst


The zebrafish belladonna (bel) mutation was identified in a large-scale mutagenesis screen to identify genes involved in retino-tectal pathfinding in Tubingen, Germany. In bel mutants, after exiting the eye, retinal axons grow ipsilaterally instead of crossing the midline to form optic chiasm. bel mutants are semi-viable and live bel embryos at 5 days show a "dilated pupil" phenotype after which the mutation was named. Later work showed that bel mutants have functional eyes although the optokinetic response is reversed in the mutants. Previous work in our lab showed that most retinal axons in the mutants initially grow towards the midline but later turn ipsilaterally. Also, two major forebrain commissures, the anterior commissure (AC) and the post-optic commissure (POC) also failed to form in bel mutants. These studies showed that bel defects are restricted to forebrain. Detailed analysis of eye sections showed defects in bel eye morphology during embryonic and adult stages. Initial work also mapped the bel locus on chromosome 8 and finer mapping linked one z-marker on either side of bel locus (z24272 and z44909). My dissertation project was to clone the bel gene and understand its role in forebrain patterning and axon guidance. I identified that bel locus encodes a zebrafish lim-homeodomain transcription factor, Lhx2. To further understand how bel(lhx2) might affect axon guidance, I first showed that bel mutants have subtle defects in forebrain patterning in the regions where axons cross the midline. I also showed that these forebrain patterning defects lead to defects in expression of proper cellular and molecular axon guidance cues at the midline in bel mutants. Finally, I showed that bel(lhx2) is required for cell proliferation in the diencephalon. Thus my detailed analysis of bel mutants has revealed new roles for lhx2 in diencephalon patterning and axon guidance.

Subject Area

Molecular biology|Neurology|Cellular biology

Recommended Citation

Seth, Anandita, "Cloning and functional characterization of the zebrafish mutation belladonna" (2005). Doctoral Dissertations Available from Proquest. AAI3193940.