Neural Rosettes

Introduction of Neural Neurulation

During embryonic development, there are a series of morphogenetic events that lead to the formation of the neural tube. Primary neurulation always occurs in the brain and most of the trunk regions. It involves several tightly orchestrated signaling pathways, such as proteins from the TGFβ/BMP family. Some studies have shown that the small molecule inhibitors (SB431542 and Noggin) against TGFβ/BMP signaling results in rapid neural conversion of hPSCs. However, the molecular mechanisms for secondary neurulation are still unknown.

Fig.1 Cell morphological changes during rosette formation. (Hříbková, 2018)

Formation of Neural Rosettes

Neural rosettes refer to radially organized cellular structures. It is the developmental characteristic of neural progenitor cells in differentiated embryonic stem cell cultures. With the formation of neural rosettes, neural tube development and neural differentiation can be modeled using human pluripotent stem cells (hPSCs) in vitro. The neural markers expressed in neural rosettes include SOX2, PAX6, and SOX1. And inhibition of BMP signaling would result in the expression of these markers and the rosette morphology. The necessary morphogenetic movements for rosette formation include intercalation, constriction, polarization, elongation, and lumen formation. During these five steps, Ca²⁺ signaling plays an important role by regulating the cytoskeletal complexes, actin, myosin II, and tubulin. In addition, neural rosettes can differentiate into distinct region-specific neurons and glia. Recent research has shown that the dismantlement of neural rosettes promotes neurogenesis and astrogenesis prematurely, which means that the complete rosette structure is essential for orderly neurodevelopment.

Fig.2 Involvement of active BMP signaling in differentiation and formation of neural rosettes. (Fedorova, 2019)

Diseases Related to Rosette Formation

The rosette formation is a histopathological hallmark for multiple tumors, such as a primitive neuroectodermal tumor, human medulloblastoma, glioblastoma, and neuroblastoma. The understanding of secondary neurulation presents great potentials for the prevention of caudal neural tube defects.

Besides, the mechanism of neural rosettes formation relates to secondary neurulation rather than that of primary neurulation. The hPSCs-based neural rosettes have been widely used as models for the research of neural tube development as well as neural differentiation in vitro.

Services at Creative Biolabs

With our neural rosette differentiation service, researchers can generate neural rosettes with high efficiency and reproducibility for their studies exploring various neurodevelopmental disorders or drug-screening applications. Our service combines years of expertise with cutting-edge technology. We fully support our clients' research needs by delivering high-quality neural rosettes and offering detailed advice on maintaining, differentiating, and characterizing these cells.

Specific services include, but are not limited to:

• Optimized protocols, culture conditions, and growth factors to ensure a high yield of homogeneous neural rosettes
• Comprehensive reports that include raw data, assay conditions, and expert interpretation of results
• Guide you through the process and provide technical support, ensuring you have the foundation to interpret, troubleshoot, and optimize requirements according to your specific research needs.

By choosing our neural rosette differentiation service, researchers can save valuable time, reduce costs, and expedite their research progress. We work closely with clients to discuss their specific requirements and customize our service to meet their precise research needs. We also offer flexibility in our services, including but not limited to:

Published Data

RF Townshend et al. reported a simple and robust protocol that triggers the formation of NPC rosettes from hPSC-derived NPC monolayers within 6 h after induction. Using this system as a platform for highly efficient quantitative and mechanistic analyses, they demonstrated that Rho/ROCK-dependent basal NPC spreading promotes NPC-rosette initiation.

They determined the induced neural rosettes at different time points from 6 to 72 hours of fixation and performed immunolocalization analysis of NPC rosettes with the indicated markers. The results demonstrated that these features of neural progenitor rosettes in which the apical contractile region of the heart is surrounded by radially organized cells are also seen in differentiated NPC rosettes.

Fig. 3 Characterization of NPC rosettes.³

Applications

Applications of our service encompass a wide range of uses in both the study and treatment of various neurological diseases, neurodevelopmental studies, and testing of therapeutics.

• Neurodevelopmental Studies: Neural rosettes are akin to the developing neuroepithelium, providing an excellent in vitro system for investigating normal and abnormal neurodevelopment, including the effects of gene mutations and environmental factors.
• In-vitro Modeling of Human Neurodevelopment: Our service provides a platform to understand the process of human neural tube formation, patterning and cell fate decisions during neurogenesis in a lab setting.
• Drug Toxicity & Efficacy Testing: We can generate neural rosettes that can be further differentiated into various neural cell types. These cells can be used to assess the potential neurotoxic effects or effectiveness of therapeutics, which can significantly speed up drug development processes.

FAQs

Q: Can you also assist with the downstream applications of neural rosettes?

A: Yes, we can certainly assist with providing guidance and support for downstream applications of differentiated neural rosettes, including neuronal differentiation, drug screening, and disease modeling. Our team has extensive experience in these fields.

Q: What kind of technical support is offered during the process?

A: We offer comprehensive technical support during the entire process. This includes regular updates on the status of differentiation, step-wise guidance, troubleshooting, and post-procedure care of the neural rosettes. We want to ensure that you are fully equipped to handle and utilize the differentiated cells for your experimental purposes.

Q: How can I place an order for the neural rosettes differentiation service?

A: You can contact us through the details provided on our website. Our customer service representative will guide you through the process, answer any queries and assist you in placing your order based on the specific requirements of your research project.

Q: What are the conditions of storage and delivery for these neural rosettes?

A: The differentiated neural rosettes are carefully packed and shipped in temperature-controlled packaging to ensure they remain viable during transit. The neural rosettes are typically shipped on dry ice in specialized containers to maintain their optimal condition. Once received, they should be stored in a freezer at a recommended temperature until you're ready to use them in your experiments.

Scientific Resources

Signaling Pathways of Neuronal Differentiation

Creative Biolabs is one of the well-recognized experts who are professional in applying advanced platforms for a broad range of neurosciences research, now we provide the novel STEMOD™ neuroscience ex vivo models for our clients all over the world. If you are interested in our services and products, please do not hesitate to contact us for more detailed information.

References

1. Hříbková, H.; et al. Calcium signaling mediates five types of cell morphological changes to form neural rosettes. Journal of cell science. 2018, 131(3).
2. Fedorova, V.; et al. Differentiation of neural rosettes from human pluripotent stem cells in vitrois sequentially regulated on a molecular level and accomplished by the mechanism reminiscent of secondary neurulation. Stem cell research. 2019, 40: 101563.
3. Townshend, Ryan F., et al. "Effect of cell spreading on rosette formation by human pluripotent stem cell-derived neural progenitor cells." Frontiers in cell and developmental biology 8 (2020): 588941.

For Research Use Only. Not For Clinical Use.