Different ophthalmologic findings in induced models of Holoprosencephaly in zebrafish

Abstract

Early forebrain development is a fascinating process and the fate of higher brain function but also the fate of visual perception largely depends on it. During gastrulation a single domain for the prospective telencephalon and a single eye field are localized in the anterior most region of the early neuroectoderm, the anterior neural plate (ANP). Importantly, these domains must be split as development proceeds, giving rise to two telencephalic lobes as well as to two optic vesicles, which are transformed into optic cups subsequently. Holoprosencephaly (HPE) unfortunately is a rather frequent developmental disorder of the forebrain, during which the separation of the early precursor domains is hampered. Clinical manifestation can vary a lot, including the accompanying ophthalmologic findings. Here we ask, whether anophthalmia is more severe than cyclopia, both being ophthalmologic findings in HPE. In this brief analysis, we make use of a recently established zebrafish model of HPE in which the early function of BMP antagonists is abrogated by the excessive induction of a BMP ligand. An early induction was resulting in retinal progenitors being stuck in the forebrain with no eye being formed. We attenuated the induction protocol to investigate whether the anophthalmia phenotype could be changed into a cyclopic phenotype. We found synophthalmia and ocular hypotelorism, however, not cyclopia. Based on this we propose that anophthalmia and cyclopia are both the strongest ophthalmologic finding, however, depending on the type of HPE underlying.