Human brain organoids assemble functionally integrated bilateral optic vesicles

During embryogenesis, optic vesicles develop from the diencephalon via a complex process of organogenesis. Using iPSC-derived human brain organoids, we attempted to simplify the complexities and demonstrate the formation of forebrain-associated bilateral optic vesicles, cellular diversity, and functionality. Around day thirty, brain organoids could assemble optic vesicles, which progressively develop as visible structures within sixty days. These optic vesicle-containing brain organoids (OVB-Organoids) constitute a developing optic vesicle's cellular components, including the primitive cornea and lens-like cells, developing photoreceptors, retinal pigment epithelia, axon-like projections, and electrically active neuronal networks. Besides, OVB-Organoids also display synapsin-1, CTIP-positive, myelinated cortical neurons, and microglia. Interestingly, various light intensities could trigger photoreceptor activity of OVB-Organoids, and light sensitivities could be reset after a transient photo bleach blinding. Thus, brain organoids have the intrinsic ability to self-organize forebrain-associated primitive sensory structures in a topographically restricted manner and can allow conducting interorgan interaction studies within a single organoid.

Genetics and functions of the retinoic acid pathway, with special emphasis on the eye

Retinoic acid (RA) is a potent morphogen required for embryonic development. RA is formed in a multistep process from vitamin A (retinol); RA acts in a paracrine fashion to shape the developing eye and is essential for normal optic vesicle and anterior segment formation. Perturbation in RA-signaling can result in severe ocular developmental diseases—including microphthalmia, anophthalmia, and coloboma. RA-signaling is also essential for embryonic development and life, as indicated by the significant consequences of mutations in genes involved in RA-signaling. The requirement of RA-signaling for normal development is further supported by the manifestation of severe pathologies in animal models of RA deficiency—such as ventral lens rotation, failure of optic cup formation, and embryonic and postnatal lethality. In this review, we summarize RA-signaling, recent advances in our understanding of this pathway in eye development, and the requirement of RA-signaling for embryonic development (e.g., organogenesis and limb bud development) and life.

Congenital Microphthalmia with Orbital Cyst: A Case Series

Microphthalmos results from incomplete invagination of the optic vesicle or closure of theembryonic fissure. We present three patients with unilateral congenital microphthalmia withcyst. None of them had vision in the affected eye since birth, with gradually increasingmass encroaching towards lower fornix and lower eyelid ectropion. On examination andinvestigations, patients had large orbital cyst with microphthalmia pushing the eyeball superiorlyand posteriorly in affected orbit. Microphthalmic globe with cyst was surgically excised andhistopathologically studied. Orbital cavity was big enough to occupy the conformer and theprosthetic eye after 6 weeks. Diagnosis was confirmed by large communicating orbital cyst withmicrophthalmia without systemic association in all the patients. None of the mothers of patientshad (antenatal care) ANC check up. All the parents had consanguineous marriage. ANC checkup with ultrasound at 14-16 weeks of pregnancy is important for genetic counselling.

Compensatory growth renders Tcf7l1a dispensable for eye formation despite its requirement in eye field specification

The vertebrate eye originates from the eye field, a domain of cells specified by a small number of transcription factors. In this study, we show that Tcf7l1a is one such transcription factor that acts cell-autonomously to specify the eye field in zebrafish. Despite the much-reduced eye field in tcf7l1a mutants, these fish develop normal eyes revealing a striking ability of the eye to recover from a severe early phenotype. This robustness is not mediated through genetic compensation at neural plate stage; instead, the smaller optic vesicle of tcf7l1a mutants shows delayed neurogenesis and continues to grow until it achieves approximately normal size. Although the developing eye is robust to the lack of Tcf7l1a function, it is sensitised to the effects of additional mutations. In support of this, a forward genetic screen identified mutations in hesx1, cct5 and gdf6a, which give synthetically enhanced eye specification or growth phenotypes when in combination with the tcf7l1a mutation.

Embryonic development of teleostBrycon orbignyanus

SummaryBrycon orbignyanusis an important large teleost that is currently on the list of endangered species, therefore studies on its reproductive biology and embryology are fundamental to help species conservation and recovery. The objective of this research was to characterize the events that occur during extrusion, fertilization and embryonic development of the species. The samples were collected at predetermined times, fixed and processed for light microscopy and scanning electron microscopy. The greenish oocytes were spherical, had translucent chorion and a mean diameter of 1.3±0.11 mm. The eggs had well defined animal and vegetative poles approximately 18 min post-fertilization. Stages from 2 to 128 blastomeres occurred between 20 min and 3 h post-fertilization (hPF), when the morula was characterized. The blastula stage was observed between 2 and 3 hPF, and the gastrula between 3 and 7 hPF, when the embryonic shield emerged and the cellular migration with the consequent formation of epiblast and hypoblast. At 8 hPF, the formation of the neural tube, above the notochord and the encephalic region, was observed, delimiting the forebrain, mesencephalon and rhombencephalon regions. From 11 hPF onward, the optic vesicle was formed close to the forebrain and the embryo tail was well developed. The optic vesicle was observed from 12 hPF onward, and the tail showed an intense movement that culminated with the rupture of the chorion and consequent hatching of the larva at 13 hPF and 27°C.