Early eye and forebrain development are facilitated by Bone Morphogenetic Protein antagonism

Vision likely is our most prominent sense and a correct development of the eye is at its basis. Early eye development is tightly connected to the development of the forebrain. A single eye field and the prospective telencephalon are situated within the anterior neural plate (ANP). If development is running correctly both are split and consecutively two optic vesicles and two telencephalic lobes emerge. If hampered, the domain is remaining condensed at the midline. This affection of development is termed Holoprosencephaly (HPE). The classical ocular finding associated with intense forms of HPE is cyclopia, one central eye. We found that antagonists of Bone morphogenetic proteins (BMP) are important to facilitate proper forebrain and eye field cleavage. Experimental induction of a BMP ligand results in HPE and the analyses of the ANP indicated a severe form. We further found anophthalmia instead of cyclopia associated with the present HPE phenotype. We identified retinal progenitors stuck in the forebrain domain, which we termed crypt-oculoid. Our data further suggest that the process of basal constriction of retinal progenitors is hampered by elevated levels of the BMP ligand. This likely is the reason for anophthalmia instead of cyclopia in this present case of HPE.