
Sonic hedgehog (SHH) is a secreted signaling factor that plays a crucial role in the molecular patterning of the central nervous system (CNS), somites, and limbs in vertebrates. SHH is involved in the generation of ventral cell types along the rostrocaudal axis of the neural tube and is secreted early in the development of the axial mesoderm and ventral neural tube. SHH also influences olfactory sensory axon growth and branching in the olfactory bulb, promoting axon branching and entry into the glomerulus. In the context of chick development, SHH is expressed in the polarizing region of the limb bud and plays a role in controlling digit number and pattern. SHH signaling is further involved in the patterning of the extracellular matrix, influencing the development of the enteric nervous system. SHH is a glycoprotein that binds to patched (Ptc) receptors on mesenchymal cells and contributes to proliferation, embryonic patterning, and cell fate determination.
| Characteristics | Values |
|---|---|
| Sonic hedgehog (SHH) | A secreted signaling factor |
| Role | Implicated in the molecular patterning of the central nervous system (CNS), somites, and limbs in vertebrates |
| Activation | Controlled by the activation of Smo downstream of Ptch1 and Boc |
| Shh-N peptide | Promotes olfactory axon branching in vitro |
| Shh protein | Transported through mitral/tufted cell dendrites |
| Shh mRNA | Expressed by mitral and tufted cells in the OB |
| Shh function | Regulates axon entry into the glomeruli and axon branching |
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What You'll Learn
- Sonic hedgehog is a secreted signalling factor that is involved in the molecular patterning of the central nervous system
- Shh protein is detected in the glomeruli of the olfactory bulb
- Shh promotes olfactory sensory axon branching and entry into the glomeruli
- Shh influences the behaviour of chick retinal ganglion cell growth cones
- Shh is involved in the patterning of neuronal connections in the visual system

Sonic hedgehog is a secreted signalling factor that is involved in the molecular patterning of the central nervous system
Sonic hedgehog (SHH) is a secreted signaling factor that plays a crucial role in the molecular patterning of the central nervous system (CNS) in vertebrates. SHH is involved in regulating embryonic morphogenesis and organogenesis, including the development of the brain, spinal cord, limbs, digits, and many other body parts.
In the context of the CNS, SHH is particularly important for the development of the neural tube, a structure that forms the groundwork for the vertebrate CNS. SHH is secreted early in development by the axial mesoderm, specifically the prechordal plate, and the notochord. It induces the formation of the floor plate, a specialized structure located at the ventral midpoint of the neural tube. This process is governed by a concentration gradient of SHH molecules, which determines different cell fates.
SHH also plays a critical role in the generation of ventral cell types along the entire rostrocaudal axis of the neural tube. Recent studies have clarified the impact of SHH signaling on dorsoventral patterning in the spinal cord, but the mechanisms in the rostral forebrain are more complex and involve separate SHH expression patterns. SHH helps establish the size, shape, and direction of cells in the brain, ensuring the normal constitution of the ventral structure.
Additionally, SHH has been found to influence the behavior of chick retinal ganglion cell growth cones and is involved in the patterning of neuronal connections in the visual system. SHH is also implicated in the emergence of oligodendrocytes in the telencephalon, suggesting a role in the olfactory bulb independent of PDGFRalpha signaling. Furthermore, SHH is detected in the glomeruli of the olfactory bulb and is involved in promoting olfactory sensory axon growth and branching, as well as their entry into the glomeruli.
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Shh protein is detected in the glomeruli of the olfactory bulb
Sonic hedgehog (Shh) is a secreted signaling factor that is crucial in the molecular patterning of the central nervous system (CNS), somites, and limbs in vertebrates. Shh is involved in the generation of ventral cell types along the rostrocaudal axis of the neural tube. It is secreted early in the development of the axial mesoderm and the ventral neural tube.
Shh plays a role in the early development of OSNs and influences their initial axon branching and innervation of the olfactory bulb. Shh also promotes the proliferation of olfactory interneuron progenitor populations in the SVZ and acts as a chemoattractant for neuroblast migration along the RMS. Shh is involved in regulating multiple cellular constituents of the glomerular circuit.
The olfactory system relies on precise circuitry connecting OSNs and appropriate relay and processing neurons of the olfactory bulb (OB). High levels of Shh signaling enable the refinement and maintenance of olfactory glomerular circuitry. Mice expressing a mutant version of Shh (ShhAla/Ala) have disproportionately small olfactory bulbs with fewer glomeruli and a loss of correspondence between individual glomeruli and specific olfactory receptors.
Shh protein is detected in the mitral cells and periglomerular interneurons of the olfactory bulb. Shh interactions with proteoglycan co-receptors regulate neurogenesis and precise olfactory connectivity, promoting functional neuronal circuitry.
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Shh promotes olfactory sensory axon branching and entry into the glomeruli
Sonic hedgehog (Shh) is a secreted signaling molecule generated by the auto-proteolytic cleavage of its precursor protein. Shh is known to play a crucial role in the generation of ventral cell types along the rostrocaudal axis of the neural tube. It is secreted early in the development of the axial mesoderm and the overlying ventral neural tube. Shh has been found to influence the behavior of chick retinal ganglion cell growth cones.
In the context of olfactory sensory axon growth, Shh has been observed to promote the branching of olfactory sensory axons and their entry into the glomeruli. Olfactory sensory neuron (OSN) axons extend from the olfactory epithelium to the olfactory bulb without branching until they reach their target region, the glomerulus. Shh protein has been detected in the glomeruli of the olfactory bulb, while its transcript is expressed in the mitral and tufted cells, indicating that Shh in the glomeruli is produced by these cells.
In primary OSN cultures, the Shh-N peptide has been shown to promote olfactory axon branching. When Shh function is neutralized in vivo using its antibody, the growth of newly generated OSN axons into the glomeruli is significantly reduced. This provides strong evidence that Shh plays a vital role in promoting olfactory sensory axon branching and their entry into the glomeruli.
Furthermore, observations in the olfactory system suggest that Shh protein is transported via mitral and tufted cell dendrites to the glomerulus, where it interacts with olfactory axon terminals. Shh has been found to be expressed in the early appearing protoglomeruli during development and persists in mature glomeruli into adulthood. While mitral and tufted cells are the primary sources of Shh, low levels of Shh transcripts have also been detected in astrocytes or juxtaglomerular neurons in the glomerular layer.
Overall, the evidence strongly suggests that Shh is a key regulator of olfactory sensory axon branching and their entry into the glomeruli, contributing to the complex process of olfactory system development.
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Shh influences the behaviour of chick retinal ganglion cell growth cones
Sonic hedgehog (SHH) is a secreted signaling factor that is crucial in the molecular patterning of the central nervous system (CNS), somites, and limbs in vertebrates. SHH is secreted early in the development of the axial mesoderm and the overlying ventral neural tube. It plays a vital role in the generation of ventral cell types along the rostrocaudal axis of the neural tube.
SHH influences the behavior of chick retinal ganglion cell growth cones. It has been discovered that SHH acts as a negative regulator of growth cone movement, suppressing the number and length of neurites extending from the chick retina. When SHH is added to cultured neurites, it reduces the intracellular level of cAMP, which is believed to be associated with the dampening of growth cone extension. This process may involve interaction with the SHH receptor, Patched, which is expressed by retinal ganglion cells.
In situ hybridization experiments on chick retina revealed low levels of Ptc1 mRNA in the retinal neuroepithelium and moderate levels in the retinal ganglion cell layer. Culturing chick retina explants and treating them with N-SHH resulted in neurite retraction and a slowdown of growth cone movement, followed by a partial retraction of the axon shaft. This growth cone collapse is reversible, as observed after washing out N-SHH and re-adding it at a later time point.
SHH is also involved in the development of the optic chiasm, influencing the location at which retinal ganglion cell axons cross. SHH induces the differentiation of ventral forebrain neurons, which may include the early differentiating neurons of the chiasm. Furthermore, SHH expression in the entire ventral midline of the early chick embryo's CNS suggests its role in guiding the outgrowth of retinal ganglion cell axons.
Overall, SHH plays a significant role in influencing the behavior of chick retinal ganglion cell growth cones, impacting the patterning of neuronal connections in the visual system.
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Shh is involved in the patterning of neuronal connections in the visual system
Sonic hedgehog (Shh) is a secreted signaling factor that plays a crucial role in the molecular patterning of the central nervous system (CNS) in vertebrates. Shh is involved in the patterning of neuronal connections in the visual system, as well as in the growth and branching of olfactory axons.
Shh is known to regulate the behavior of retinal ganglion cell growth cones, which are found in the visual system. This regulation plays a significant role in the patterning of neuronal connections. Traiffort et al. provided the first evidence of Shh axonal transport by demonstrating that a radioactive signal could be detected in the superior colliculus after injecting a radio-labelled Shh into the eye.
In the olfactory system, Shh is involved in promoting the growth and branching of olfactory sensory neuron (OSN) axons and their entry into the glomeruli. Shh protein is produced by mitral and tufted cells and is transported through their dendrites to the glomerulus, where it interacts with olfactory axon terminals. When Shh function is neutralized, the growth of newly generated OSN axons into the glomeruli is significantly reduced.
Shh signaling is highly dynamic in the nervous system, ranging from canonical transcription-dependent processes to non-canonical localized activities at axonal growth cones. Shh signaling mechanisms vary depending on the maturational state of the responsive cell, other signaling pathways regulating neural cell function, and environmental cues surrounding target cells.
Shh also plays a crucial role in the generation of ventral cell types along the rostrocaudal axis of the neural tube. It is secreted early in development by the axial mesoderm and the overlying ventral neural tube. Shh signaling pathways have been studied extensively in the context of neural tube patterning, and its interactions with other signaling molecules, such as fibroblast growth factor 8 (FGF8), have been observed to influence neuronal commitment and differentiation.
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Frequently asked questions
It is a secreted signaling factor that is involved in the molecular patterning of the central nervous system (CNS), somites, and limbs in vertebrates.
SHH is detected in the glomeruli of the olfactory bulb, and its transcript is expressed in the mitral and tufted cells. SHH promotes olfactory sensory axon branching and entry into the glomeruli.
SHH is expressed in the polarizing region of the limb bud, controlling digit number and pattern. Application of SHH protein to early limb buds can mimic polarizing region signaling, and its application to regions between digit primordia can induce changes in digit morphogenesis. SHH also plays a role in the development of the enteric nervous system and axon guidance.











































