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  在20世紀70年代,發育生物學的基本問題是一個相對簡單的受精卵是如何發展成一個複雜的身體分節的動物的。70年代末,克里斯汀·紐斯林-沃爾哈德和艾瑞克·威斯喬斯分離了控制果蠅前後體軸發育分節的突變基因,他們的“飽和誘變”技術導致了一系列參與體軸形態發生基因的發現。1995年,他們因在對果蠅胚胎髮育基因突變的研究工作與愛德華·路易斯共同獲得諾貝爾獎。  黑腹果蠅的刺蝟 ("hh") 基因被發現為其中一種可以造成個體體節前後差異的重要基因。果蠅的刺蝟基因在1992年分別被 Jym Mohler, Philip Beachy, 以及 Thomas B. Kornberg的實驗室所複製出來。 若其中一些刺蝟基因發生突變,將會造成相較於野生型來說,較為短小且矮胖的不正常形狀胚胎。刺蝟基因的功能為影響體節極性,其突變會會影響幼體的表皮棘刺和成體的附支,如腿和觸角。Rather than the normal pattern of denticles, hedgehog mutant larvae tend to have "solid lawns" of denticles (Figure 1). 刺蝟基因突變的果蠅幼蟲具有短小且多毛的特徵,形似刺蝟,故此得名。

  

  昆蟲細胞表達全長含有鋅指的轉錄因子Ci蛋白, 而此蛋白會在細胞質中和類似kinesin蛋白Costal-2 (Cos2) 形成複合體並結合到微管上(圖2)。 對155 kDa全長Ci蛋白的依賴於蛋白酶體的剪下產生75 kDa片段(CiR)。CiR在細胞內累計並擴散到細胞核,在那裡它作為刺蝟因子靶基因的共。 The steps leading to Ci protein proteolysis include phosphorylation of Ci protein by several protein kinases; PKA, GSK3β and CK1 (Figure 2). The "Drosophila" protein Slimb is part of an SCF complex that targets proteins for ubiquitylation. Slimb binds to phosphorylated Ci protein.  In the absence of Hh (圖 3), a cell-surface transmembrane protein called Patched (PTCH) acts to prevent high expression and activity of a 7 membrane spanning receptor called Smoothened (SMO). Patched has sequence similarity to known membrane transport proteins. When extracellular Hh is present (Figure 3), it binds to and inhibits Patched, allowing Smoothened to accumulate and inhibit the proteolytic cleavage of the Ci protein. This process most likely involves the direct interaction of Smoothened and Costal-2 and may involve sequestration of the Ci protein-containing complex to a microdomain where the steps leading to Ci protein proteolysis are disrupted. The mechanism by which Hh binding to Patched leads to increased levels of Smoothened is not clear (Step 1 in Figure 3). Following binding of Hh to Patched, Smoothened levels increase greatly over the level maintained in cells when Patched is not bound to Hh. It has been suggested that phosphorylation of Smoothened plays a role in Hh-dependent regulation of Smoothened levels.  In cells with Hh-activated Patched (Figure 3), the intact Ci protein accumulates in the cell cytoplasm and levels of CiR decrease, allowing transcription of some genes such as decapentaplegic (dpp, a member of the BMP growth factor family). For other Hh-regulated genes, expression requires not only the loss of CiR but also the positive action of uncleaved Ci to act as a transcriptional activator. Costal-2 is normally important for holding Ci protein in the cytoplasm, but interaction of Smoothened with Costal-2 allows some intact Ci protein to go to the nucleus. The "Drosophila" protein Fused (Fu in Figure 3) is a protein kinase that binds to Costal-2. Fused can inhibit Suppressor of Fused (SUFU), which in turn interacts with Ci to regulate gene transcription in some cell types.

  Hedgehog has roles in larval body segment development and in formation of adult appendages. During the formation of body segments in the developing "Drosophila" embryo, stripes of cells that synthesize the transcription factor Engrailed can also express the cell-to-cell signaling protein Hedgehog (green in Figure 4). Hedgehog is not free to move very far from the cells that make it and so it only activates a thin stripe of cells adjacent to the Engrailed-expressing cells. When acting in this local fashion, hedgehog works as a paracrine factor. Only cells to one side of the Engrailed-expressing cells are competent to respond to Hedgehog following interaction of Hh with the receptor protein Patched (blue in Figure 4).  Cells with Hh-activated Patched receptor synthesize the Wingless protein (red in Figure 4). If a "Drosophila" embryo is altered so as to produce Hh in all cells, all of the competent cells respond and form a broader band of Wingless-expressing cells in each segment. The "wingless" gene has an upstream transcription regulatory region that binds the Ci transcription factor in a Hh-dependent fashion resulting in an increase in "wingless" transcription (interaction 2 in Figure 3) in a stripe of cells adjacent to the stripe of Hh-producing cells.  Wingless protein acts as an extracellular signal and patterns the adjacent rows of cells by activating its cell surface receptor Frizzled. Wingless acts on Engrailed-expressing cells to stabilize the stripes of Engrailed expression. Wingless is a member of the Wnt family of cell-to-cell signaling proteins. The reciprocal signaling by Hedgehog and Wingless stabilizes the boundary between parasegments (Figure 4, top). The effects of Wingless and Hedgehog on other stripes of cells in each segment establishes a positional code that accounts for the distinct anatomical features along the anterior-posterior axis of the segments  The Wingless protein is called "wingless" because of the phenotype of some "wingless" fly mutants. Wingless and Hedgehog functioned together during metamorphosis to coordinate wing formation. Hedgehog is expressed in the posterior part of developing "Drosophila" limbs. Hedgehog also participates in the coordination of eye, brain, gonad, gut and tracheal development. Hedgehog has been implicated in reduced eye development in the amphipod Gammarus minus. Specifically, downregulation of hedgehog results in reduced eyes.

  

  胚胎髮育時缺少刺蝟因子(因基因突變或孕婦誤食致畸劑)都會導致嚴重的發育異常。
刺蝟訊號通路(英語:Hedgehog signaling pathway)是重要的訊號傳導通路。