Holoprosencephaly and cyclopia in and Crispant zebrafish.

Holoprosencephaly (HPE) is the most frequent developmental disorder of the forebrain. In HPE, the early single anlage of the forebrain, the anterior neural plate (ANP) which encompasses the future telencephalon and eye field, fails to divide. BMP signaling and antagonism are overall important for nervous system development. The focus of this study was on the role of the ligand and the receptor during forebrain development. The zebrafish loci of and were targeted transiently with CRISPR/Ca9. Crispants for both and presented HPE and cyclopia, one central eye. Subsequently, the ANP was addressed in Crispants. The morphology of the eye field was affected, with important markers, , and expressed condensed at the midline. Induced expression of is also known to result in HPE. Such induction altered the expression of . Zebrafish Crispants for and can be used as a novel HPE model. A challenge in future analyses will be the penetrance of phenotypes in Crispants. The advantages are, however, that analyses can be conducted anywhere, without the need of mutant lines. One important aspect for future analysis will be the role of individual bmp ligands, receptors and antagonists in forebrain development.