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The relationship between sonic Hedgehog signaling, cilia, and neural tube defects.

The Hedgehog signaling pathway is essential for many aspects of normal embryonic development, including formation and patterning of the neural tube. Absence of the sonic hedgehog (shh) ligand is associated with the midline defect holoprosencephaly, whereas increased Shh signaling is associated with exencephaly and spina bifida. To complicate this apparently simple relationship, mutation of proteins required for function of cilia often leads to impaired Shh signaling and to disruption of neural tube closure. In this article, we review the literature on Shh pathway mutants and discuss the relationship between Shh signaling, cilia, and neural tube defects.