Sonic Hedgehog in Neural Patterning

Introduction to Sonic Hedgehog

Sonic hedgehog is a type of signaling molecule that is critical for regulating embryonic development in various species. Normally, the sonic hedgehog can be secreted by different kinds of cells or proteins, such as epithelial cells and smoothened proteins. Pilot studies have shown that protein patched homolog 1 (PTC1) can bind to smoothened (SMO) proteins to further control its release. In this condition, SMO protein can activate the GLI transcription factors to mediate many morphogenetic processes. Sonic hedgehog can be expressed in some posterior intestinal structures, such as the cloacal epithelium, where it binds to the surrounding mesenchymal tissue. Moreover, the sonic hedgehog can mediate the differentiation, proliferation, and apoptosis of epithelial and mesenchymal cells by inducing GLI2. Also, the sonic hedgehog plays an important role in the formation of the prostate and the development of external genitalia.

Fig.1 The sonic hedgehog gradient in embryonic neural patterning. (Lee, 2011)

Sonic Hedgehog in Neural Patterning

The sonic hedgehog signaling pathway is one of the main pathways regulating the development of multiple tissue development. Abnormalities of sonic hedgehog signaling pathways are associated with birth defects, tissue renewal, as well as cancer development. In general, the activation of sonic hedgehog signaling needs the binding of the Ptc/smo receptor complex and the induction of signal transduction cascade reactions. Specifically, the binding of the sonic hedgehog with this complex produces a series of intracellular signals, regulates certain types of protein kinases, and activates a group of transcription factors, such as glioblastoma (Gli) proteins.

Furthermore, recent reports have revealed that the regulation action of sonic hedgehog signaling is essential for central nervous system (CNS) polarity and neural patterning. A sonic hedgehog signaling molecule is involved in a variety of neuronal cell differentiation in the process of neural tube development. For the induction of different cell types, the secreted sonic hedgehog protein will be treated as a morphogen. Different concentrations of the sonic hedgehog protein can be used to produce specific cells, which will be distributed in a gradient at different synthesis sites. Several molecules on the surface of the neuroepithelial cell have been identified that can be used for the transportation and gradient distribution of sonic hedgehog protein. Besides, two transcription factors, GLI2 and GLI3, can regulate the function inside the responding cells to trigger the stereotypic ventral cell differentiation in neural patterning.

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Reference

1. Lee, R. W.; et al. Hypothesis: the role of sterols in autism spectrum disorder. Autism research and treatment. 2011.