Holoprosencephaly and Cyclopia in bmp7b and bmpr1ba Crispant zebrafish

Abstract

The visual system is highly specialized and its function is substantially depending on the proper development of the eyes. Early eye development starts with the definition of a single eye field, which is localized within the anterior neural plate (ANP). This single eye field is split consecutively and two optic vesicles emerge at the sides. These vesicles are then transformed into optic cups, out of which the future retinae are differentiating. Holoprosencephaly (HPE) is a frequent developmental forebrain disorder, in which the splitting of ANP domains is hampered. HPE is mostly genetically linked and we recently showed that BMP antagonism is important for the eye field and the telencephalic anlage to split. Excessive BMP induction led to retinal progenitors stuck inside a dysmorphic forebrain. In this study, using the zebrafish as a model, we show with acute CRISPR/ Cas9 analysis in the F0 generation, the necessity of bmp7b and bmpr1ba for proper forebrain development. In Crispants for both genes we found HPE phenotypes, e.g. cyclopia. Further analysis of bmp7b Crispants indicated that predominantly the eye field is affected, rather than the telencephalic precursor domain.