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The hedgehog signaling pathway is one of several complicated cell signaling systems present in multicellular animals, and it plays a critical role in developmental biology. It is found in both vertebrates and invertebrates, as will be discussed more below, and is a heavily researched area of human embryological development for the differentiation of cells and tissues into the brain and heart.
Mitogenesis, or the stimulation of cell division, is a primary result of hedgehog signaling. The process by which cells divide has a significant influence on differentiation and organ development. Abnormalities in this pathway can result in significant birth defects or tumor development.
Mammals have three Hedgehog homologues: Desert (DHH), Indian (IHH), and Sonic (SHH), the latter of which has received the most attention. Because the route is critical during vertebrate embryonic development, it is of relevance in evolutionary developmental biology.
A fundamental problem in developmental biology in the 1970s was understanding how a very basic egg might give rise to a complicated segmented body design. Christiane Nüsslein-Volhard and Eric Wieschaus identified mutations in genes that affect the formation of the fly's segmented anterior-posterior body axis in the late 1970s. Their "saturation mutagenesis" technique led to the discovery of a set of genes involved in body segmentation development, laying the groundwork for the study of evolutionary developmental biology. Formal paraphrase In 1995, they shared the Nobel Prize in Physiology or Medicine with Edward B. Lewis for their work on genetic alterations in Drosophila embryogenesis.
Hh activity induces further expression of its transmembrane receptor Ptc, thus simultaneously initiating signalling while restricting the range of movement by sequestering Hh protein. Another cell-surface protein that binds to and sequesters Hh, HIP1,is also up-regulated by pathway activation, thus serving to down-regulate Hh activity.
Hedgehog protein (Hh) activates the signaling pathway by acting as a chemical mediator to initiate signal transduction. Sonic hedgehog (Shh), Indian hedgehog (Ihh), and Desert hedgehog are the three primary hedgehog proteins found in vertebrates (Dhh). All of these mediator proteins stimulate the same cell signaling pathway, yet they each activate distinct development genes.
The mechanism begins when Shh binds and inactivates a transmembrane protein called Patched (Ptch). After the binding of Shh, Ptch is sent into the cell and degraded by the proteasome. Ptch normally inhibits another protein called Smoothened (Smo), found within the cell inside a vesicle. The degradation of Ptch leads Smo to migrate from the vesicle and embed in the membrane.
This causes the activation of a critical collection of proteins known as Gli proteins. Gli proteins migrate into the cell nucleus after being activated by Smo and operate as transcription factors, turning on genes that favor development and turning off those that do not.
Abnormalities or mutations in this signaling system can frequently result in birth defects owing to developmental mistakes in embryos, as well as tumor formation owing to uncontrolled tissue growth.
Basal cell carcinoma, a common kind of cancer, is frequently caused by a loss of functioning Patched protein, which actively opposes the stimulation of genes involved in cell growth and development. The absence of this protein efficiently activates the hedgehog signaling pathway, resulting in uncontrolled cell proliferation and tumor formation.