Biology subjects

Rensinghoff, P.

Publications and source records attributed to Rensinghoff, P..

2 recordsLinked to original sources

bioRxiv2024

Holoprosencephaly and Cyclopia in bmp7b and bmpr1ba 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 bmp7b and the receptor bmpr1ba during forebrain development. The zebrafish loci of bmp7b and bmpr1ba were targeted transiently with CRISPR/Ca9. Crispants for both bmp7b and bmpr1ba presented HPE and cyclopia, one central eye. Subsequently, the ANP was addressed in bmp7b Crispants. The morphology of the eye field was affected, with important markers, rx3, six3b and cxcr4a expressed condensed at the midline. Induced expression of bmp4 is also known to result in HPE. Such bmp4 induction altered the expression of bmpr1ba. Zebrafish Crispants for bmp7b and bmpr1ba can be used as a novel HPE model. A challenge in future analyses will be the penetrance of phenotypes in Crispants. 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.

developmental biology↗

bioRxiv2022

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.

developmental biology↗