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Bulk, J.

Publications and source records attributed to Bulk, J..

4 recordsLinked to original sources

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↗

Different ophthalmologic findings in induced models of Holoprosencephaly in zebrafish

Early forebrain development is a fascinating process. The fate of brain function but also the fate of visual perception largely depends on it. Holoprosencephaly (HPE) is the most frequent developmental disorder of the forebrain, during which the separation of the early precursor domains is hampered. A spectrum of clinical manifestations is seen with severe forms like alobar HPE and less severe forms like lobar HPE. The ophthalmologic findings which accompany HPE are also found as a spectrum that ranges from ocular hypotelorism and synophthalmia to cyclopia and anophthalmia. Here we ask, whether anophthalmia or cyclopia is the default ophthalmologic finding in severe forms of HPE. In this brief analysis, we made use of a recently established zebrafish model of severe HPE, based on BMP ligand induction. Such BMP ligand induction resulted in anophthalmia. We attenuated the induction protocol to investigate whether the anophthalmia phenotype could be changed into a cyclopic phenotype. We found a spectrum of ocular phenotypes, ocular hypotelorism, and also cases of synophthalmia and cyclopia. This suggests that in the context of this HPE model the strongest ophthalmologic phenotype is anophthalmia and less severe forms are cyclopia, synophthalmia and ocular hypotelorism.

developmental biology↗

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↗

Cockroaches show individuality in learning and memory during classical and operant conditioning

Animal personality and individuality are intensively researched in vertebrates and both concepts are increasingly applied to behavioral science in insects. However, only few studies have looked into individuality with respect to performance in learning and memory tasks. In vertebrates individual learning capabilities vary considerably with respect to learning speed and learning rate. Likewise, honeybees express individual learning abilities in a wide range of classical conditioning protocols. Here, we study individuality in the learning and memory performance of cockroaches, both in classical and operant conditioning tasks. We implemented a novel classical (olfactory) conditioning paradigm where the conditioned response is established in the maxilla-labia response (MLR). Operant spatial learning was investigated in a forced two-choice task using a T-maze. Our results confirm individual learning abilities in classical conditioning of cockroaches that was reported for honeybees and vertebrates but contrast long-standing reports on stochastic learning behavior in fruit flies. In our experiments, most learners expressed a correct behavior after only a single learning trial showing a consistent high performance during training and test. We can further show that individual learning differences in insects are not limited to classical conditioning but equally appear in operant conditioning of the cockroach.

animal behavior and cognition↗