High Wnt signaling establishes the dorsal region while high Shh signaling indicates the ventral region. Cyclopamine impacts embryonic development by hindering the sonic hedgehog (Shh) pathway. Sonic hedgehog is a protein that in humans is encoded by the "SHH" gene. A gradient of BMP signaling is found in opposition to a Sonic hedgehog, Shh, gradient. FGF/Shh signaling, deriving from the periphery. The exposure to SHH leads to differentiation of thalamic neurons. In a knockout gene model, absence of SHH is indicative of holoprosencephaly. ZRS is a noncoding element, 800 kilobasepairs remote to the target gene Shh. These transcription factors respond to SHH gradient concentration. Shh induces the AER to produce FGF4 and FGF8 which maintains the expression of Shh. Gene symbols are italicised and all letters are in lowercase ("shh"). Gene symbols are italicised, with all letters in lowercase ("shh"). Healthy brain development is also dependent on the signaling function of SHH. SHH mutant phenotype can be rescued in SHH/Gli3 double mutant. It is the result of abnormal activity by the protein SHH (sonic hedgehog).