# Ophthalmologic Findings in an Induced Model of Holoprosencephaly in Zebrafish

## TL;DR

This study uses zebrafish to model holoprosencephaly and finds a range of eye abnormalities that mirror the human condition.

## Contribution

The study demonstrates a variable ophthalmologic phenotype spectrum in a zebrafish model of HPE by modulating BMP4 induction.

## Key findings

- Attenuated BMP4 induction in zebrafish leads to a spectrum of ocular phenotypes including hypotelorism and cyclopia.
- Phenotype severity correlates with the timing and duration of BMP4 induction during embryonic development.
- The model replicates key features of the human HPE ophthalmologic spectrum.

## Abstract

Holoprosencephaly (HPE) is the most frequent developmental disorder of the forebrain. In this condition, the separation of the early precursor domains is hampered. A spectrum of clinical manifestations can be observed, for example, severe forms like alobar HPE and less severe forms like lobar HPE. Ophthalmologic findings that accompany HPE also occur as a spectrum that ranges from ocular hypotelorism and synophthalmia to cyclopia and anophthalmia. In this brief analysis, we made use of a recently established zebrafish model of HPE. This model is based on experimental BMP ligand induction that resulted in anophthalmia. We attenuated the induction protocol to investigate whether the ophthalmologic phenotype can also be attenuated. We found a spectrum of ocular phenotypes: ocular hypotelorism, cases of synophthalmia, and cyclopia.

We used a zebrafish (Danio rerio) model to variably induce bmp4 during embryonic development. We show ophthalmologic phenotypes of variable severity depending on the length and onset of bmp4 inductions. We find phenotypes like ocular hypotelorism, synophthalmia, cyclopia, and anophthalmia, which are described to be part of the HPE spectrum.