2016 Group Project 4-1

2016 Student Projects
Signalling: 1 Wnt | 2 Notch | 3 FGF Receptor | 4 Hedgehog | 5 T-box | 6 TGF-Beta
2016 Group Project Topic - Signaling in Development OK you are now in a group, add a topic with your student signature to the group page.
This page is an undergraduate science embryology student project and may contain inaccuracies in either descriptions or acknowledgements.

Group Assessment Criteria
Science Student Projects The key points relating to the topic that your group allocated are clearly described. The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area. Content is correctly cited and referenced. The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations. Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities. Relates the topic and content of the Wiki entry to learning aims of embryology. Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer's wiki. Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement. The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning. Develops and edits the wiki entries in accordance with the above guidelines.
More Information on Assessment Criteria | Science Student Projects

Hedgehog Signalling Pathway

Introduction

An image of a hedgehog, the animal of which the Hh proteins are named after.

The Hedgehog (Hh) signalling pathway is an important part of the early embryo with regards to the patterning and development of the nervous system, limbs and the cranio-facial region in vertebrates and the polarization of the segments in the Drosophila embryo. It was first identified in 1980 by Christiane Nüsslein-Volhard and Eric Wieschaus, alongside a group of other genes regulating segment polarity in Drosophila embryonic development. The pathway itself consists of Hh proteins, where there are three identified homologs in vertebrates, being sonic hedgehog (SHH), Indian hedgehog (IHH), and desert hedgehog (DHH) . All homologs are expressed at varying levels within different tissues in the body, and also act as a form of redundancy to an extent between one another.

The signaling pathway is highly conserved between various species. and acts via a G protein coupled receptor like receptor, which uninhibited via the action of the Hh proteins. The pathway overall acts via a balance of dephosphorylation and degradation of proteins in order to regulate transcription factor activity to express various genes to carry out its action. The Hh pathway is also highly implicated when it comes to abnormalities in development, as it is implicated in diseases such as holoprosencephaly and cleft lip and palate. Overall Hh signaling pathways play a large role in embryological development, which will be discussed in detail on this page.

History

1980	Christiane Nüsslein-Volhard and Eric Wieschaus first identified a group of genes including those related to the Hedgehog signalling pathway and linked them to the segmentation and planning of the embryo in Drosophila melanogaster by introducing mutagenic substances to the developing embryo.
1993	Multiple researchers including Andrew P. McMahon and Clifford Tabin discovered three equivalent homologs in vertebrates of the Drosophila melanogaster hedgehog gene, known as sonic hedgehog (Shh), desert hedgehog (Dhh) and indian hedgehog (Ihh), by looking at DNA sequences similar to that of the gene in the fruit fly.
1993	Clifford Tabin and his lab identified the role of Shh in localising the limb bud, where they identified protein to be expressed within a region of the limb bud known as the zone of polarising activity (ZPA), showing that SHH is sufficient to induce the production of a ZPA, and thus limb bud formation in chick embryos.
1995	Sonic hedgehog secreted by the notochord was identified to induce ventral cell types in the neural tube during embryonic development, most notably the floor plate cells and the motor neurons as shown in chick embryos. Such differentiation between the two cell types is thought to be a matter of sonic hedgehog concentrations experienced by the neural plate cells.
1995	A shared Nobel prize in physiology or medicine was awarded to Christiane Nüsslein-Volhard and Eric Wieschaus for their researching regarding the identification of the developmental genes relating to the formation and patterning of the early embryo via genes.
1996	Studies showed that human homologs of the Patched gene, a component of the hedgehog pathway, is a key gene that is mutated in Gorlin Syndrome, which characterised by a predisposition for basal cell carcinomas, the most common cancers in humans and developmental abnormalities.
1999	Researchers implicated Indian hedgehog as a key signalling molecule for the maturation and differentiation of prehypertrophic chondrocytes, where Indian hedgehog null mice were shown to have a lack of mature chondrocytes and no development of osteoblast cells in endochondrial bone. This was thought to be due to Indian hedgehog having a feedback signal controlling parathyroid hormone related protein, which regulates endochondrial bone development.
2003	Sonic hedgehog was identified to regulate the proliferation of adult neural stem cells as shown in the hippocampus of rats and in vitro for neural progenitor cells isolated from the hippocampus.
2003	Studies on Shh function found that it can act as a chemoattractant in the developing embryo spinal cord, to help guide commissural axons to the midline of the floor plate.
2009	Mouse models showed that reduction in hedgehog signalling allows for transient improved response to chemotherapy with regards to mouse models of human pancreatic ductal adenocarcinoma, a cancer with one of the highest mortality rates in humans.