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.

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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.

For Research Use Only. Not For Clinical Use.