In this context Shh acts as a morphogen-it induces cell differentiation dependent on its concentration.

Also, the position at which these neuronal groups are generated in vivo can be predicted by the concentration of Shh required for their induction in vitro.

Shh exerts its effects in a concentration-dependent manner, so that a high concentration of Shh results in a local inhibition of cellular proliferation.

Lower concentration of Shh results in cellular proliferation and induction of various ventral neural cell types.

Once the floor plate is established, cells residing in this region will subsequently express Shh themselves generating a concentration gradient within the neural tube.

In vitro studies show that incremental two-threefold changes in Shh concentration give rise to motor neuron and different interneuronal subtypes as found in the ventral spinal cord.

The graded concentration of Shh gives rise to graded acitivity of Gli 2 and Gli3, which promote ventral and dorsal neuronal subtypes in the ventral spinal cord.

These transcription factors respond to Shh gradient concentration.

Evidence supporting this comes from studies done using BMP inhibitors which ventralize the fate of the neural plate cell for a given Shh concentration.

The concentration and time dependent cell fate determining activity of Shh in the ventral neural tube makes it a prime example of a morphogen.

Shh emanates from the notochord and ventral floor plate of the developing neural tube to create a concentration gradient that spans the dorso-ventral axis.

It is thought that the Shh gradient works to elicit multiple different cell fates by a concentration and time dependent mechanism that induces a variety of transcription factors in the ventral progenitor cells.

These transcription factors are induced sequentially along the Shh concentration gradient with respect to the amount and time of exposure to Shh ligand.

Early in development the cells at the ventral midline have only been exposed to a low concentration of Shh for a relatively short time and express the transcription factor Olig2.

It is in this way that each of domains of the six progenitor cell populations are thought to be successively patterned throughout the neural tube by the Shh concentration gradient.

The following is a proposed mechanism for how Shh patterns the ventral neural tube: A gradient of Shh is created which controls the expression of a group of homeodomain ( HD ) and basic Helix-Loop-Helix ( bHLH ) transcription factors.

Shh secreted from the floor plate creates a gradient along the ventral neural tube.

Although there is no direct evidence of a Shh gradient, there is indirect evidence via the visualization of Patched ( Ptc ) gene expression, which encodes for the ligand binding domain of Shh receptor, throughout the ventral neural tube.

These incremental changes in vitro correspond to the distance of domains from the signaling tissue ( notochord and floor plate ) which subsequently differentiates into different neuronal subtypes as it occurs in vitro. Shh gradient and Gli activity in the vertebrate neural tube.

Each of the ventral progenitor domains expresses a highly individualized combination of transcription factors: Nkx2. 2, Olig2, Nkx6. 1, Nkx 6. 2, Dbx1, Dbx2, Irx3, Pax6, and Pax7, that is regulated by the Shh gradient.

The expression of Olig2 rapidly expands in a dorsal direction concomitantly with the continuous dorsal extension of the Shh gradient over time.

In mice, the function of signaling at the MDO has not been addressed directly due to a complete absence of the diencephalon in Shh mutants.

It has been demonstrated that Shh attracts commissural axons at the ventral midline of the developing spinal cord.

The absence ( non-expression ) of Shh has been shown to control the growth of nascent hind limbs in cetaceans ( whales and dolphins ).

This has subsequently been adopted by other students ' unions around the UK, although in many instances the expansion of the abbreviation has been dropped, leaving campaigns called " Shh ", " Sshh ", or variants.

Although expression of Shh pathway proteins has not been reported to oscillate in the PSM, they are expressed within the PSM during somitogenesis.

Interaction of Shh with Fgf and RA have yet not been studied in molecular detail.

Netrin is important in patterning of the neural system in chordates, as well as is the molecule Shh, but S. kowalevskii was only found to have one hh gene and it appears to be expressed in a region that is uncommon to where it is usually expressed in developing chordates along the ventral midline.

The ventral neural tube is patterned by Sonic Hedgehog ( Shh ) from the notochord, which acts as the inducing tissue.

Floor plate-derived Shh subsequently signals to other cells in the neural tube, and is essential for proper specification of ventral neuron progenitor domains.

These cell types are specified by the secretion of Shh from the notochord ( located ventrally to the neural tube ), and later from the floor plate cells.

Studies have shown that neural progenitors can evoke different responses based on the length of exposure to Shh, with a longer exposure time resulting in more ventral cell types.

BMP from the dorsal end of the neural tube seems to act in the same concentration-dependent manner as Shh in the ventral end.

The mouse open brain ( opb ) and Sonic hedgehog ( Shh ) genes have opposing roles in neural patterning: opb is required for dorsal cell types and Shh is required for ventral cell types in the spinal cord.

One of the most characterized functions of Shh is its role in the induction of the floor plate and diverse ventral cell types within the neural tube .< ref name =" pmid11002335 "> The notochord, a structure derived from the axial mesoderm, produces Shh which travels extracellularly to the ventral region of the neural tube and instructs those cells to form the floor plate.

Vitronectin is another protein that is induced by Shh and it acts as an obligate co-factor for Shh signaling in the neural tube.

It is important to note that Shh is not the only signaling molecule exerting an effect on the developing neural tube.

Many other molecules, pathways, and mechanisms are active ( e. g. RA, FGF, BMP ), and complex interactions between Shh and other molecules are possible. BMPs are suggested to play a critical role in determining the sensitivity of neural cell to Shh signaling.

In vertebrates, Shh signaling in the ventral portion of the neural tube is most notably responsible for the induction of floor plate cells and motor neurons.

Higher concentrations of the Shh ligand are found in the most ventral aspects of the neural tube and notochord, while lower concentrations are found in the more dorsal regions of the neural tube.

In addition, studies on chick and mice have shown that blocking the Shh pathway leads to absence of the rostral thalamus and substantial decrease of the caudal thalamus.

On the other hand, mice mutant for Shh lack ventral spinal cord characteristics. In vitro blocking of Shh signaling using antibody against it shows similar phenotypes.