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Orofacial clefts such as cleft lip and/or palate are common structural birth defects with birth prevalence ranging from 1/500 to 1/2,000 in different populations. Their complex etiology is not fully understood and both genetic and environmental causes have been established to be involved in cleft lip and/or palate development. Many genes have been found to be involved or correlate with cleft occurrence. One pivotal gene appears to be located on chromosome 1 at the  1q32 region, which encodes interferon regulatory factor-6 (IRF6)<ref><pubmed>15185170</pubmed></ref>, an important member of the IRF family involved in oral and maxillofacial development<ref><pubmed>23940636</pubmed></ref>. The failure in growth of the frontonasal prominence, the paired mandibular processes, the paired maxillary processes, and the medial and lateral nasal processes in week 4, together with the failure in fusion of the lateral nasal processes with the maxillary processes, and the medial nasal processes in week 6 and 7 results in orofacial clefting of the upper lip and/or primary palate. Clefts in the secondary palate may arise due to failure in several developmental steps after week 6, such as palatal shelves elevation or migration<ref><pubmed>24124047</pubmed></ref>.
Orofacial clefts such as cleft lip and/or palate are common structural birth defects with birth prevalence ranging from 1/500 to 1/2,000 in different populations. Their complex etiology is not fully understood and both genetic and environmental causes have been established to be involved in cleft lip and/or palate development. Many genes have been found to be involved or correlate with cleft occurrence. One pivotal gene appears to be located on chromosome 1 at the  1q32 region, which encodes interferon regulatory factor-6 (IRF6)<ref><pubmed>15185170</pubmed></ref>, an important member of the IRF family involved in oral and maxillofacial development<ref><pubmed>23940636</pubmed></ref>. The failure in growth of the frontonasal prominence, the paired mandibular processes, the paired maxillary processes, and the medial and lateral nasal processes in week 4, together with the failure in fusion of the lateral nasal processes with the maxillary processes, and the medial nasal processes in week 6 and 7 results in orofacial clefting of the upper lip and/or primary palate. Clefts in the secondary palate may arise due to failure in several developmental steps after week 6, such as palatal shelves elevation or migration<ref><pubmed>24124047</pubmed></ref>.


Mutations in IRF6 were first identified in patients suffering from Van der Woude syndrome, who often display orofacial clefts in addition to other symptoms. In several subsequent research studies SNPs in IRF6 were also detected in non-syndromic cleft lip and/or palate<ref><pubmed>21331089</pubmed></ref>. The phenotypic heterogeneity of Van der Woude syndrome in comparison to non-syndromic cleft lip and/or palate is hypothesized to be caused by different types of mutations of IRF6 resulting in either a partially or fully nonfunctional protein<ref><pubmed>22438645</pubmed></ref>. In addition, the phenotype might be influenced by the site of mutation<ref><pubmed>23949966</pubmed></ref>. Mutations on a specific sequence variant about ten kb upstream of its transcription start site have been found to keep transcription factor AP-2α from binding and, therefore, influencing IRF6 expression<ref name=21331089/>.
Mutations in IRF6 were first identified in patients suffering from Van der Woude syndrome, who often display orofacial clefts in addition to other symptoms. In several subsequent research studies SNPs in IRF6 were also detected in non-syndromic cleft lip and/or palate<ref><pubmed>21331089</pubmed></ref>. The phenotypic heterogeneity of Van der Woude syndrome in comparison to non-syndromic cleft lip and/or palate is hypothesized to be caused by different types of mutations of IRF6 resulting in either a partially or fully nonfunctional protein<ref><pubmed>22438645</pubmed></ref>. In addition, the phenotype might be influenced by the site of mutation<ref><pubmed>23949966</pubmed></ref>. Mutations on a specific sequence variant about ten kb upstream of its transcription start site have been found to keep transcription factor AP-2α from binding and, therefore, influencing IRF6 expression<refname=21331089/>.


There are several hypotheses how IRF6 irregularities may affect development on a molecular level derived from various animal models. IRF6 mutations caused a hyper-proliferative epidermis in mice. This will induce a failure of terminal differentiation in the respective epidermis and generate epithelial adhesions that can clog the oral cavity and create a cleft palate. IRF6 also has been identified as a key determinant of keratinocyte proliferation, oral periderm formation, and its spatio-temporal regulation.
There are several hypotheses how IRF6 irregularities may affect development on a molecular level derived from various animal models. IRF6 mutations caused a hyper-proliferative epidermis in mice. This will induce a failure of terminal differentiation in the respective epidermis and generate epithelial adhesions that can clog the oral cavity and create a cleft palate. IRF6 also has been identified as a key determinant of keratinocyte proliferation, oral periderm formation, and its spatio-temporal regulation.

Revision as of 18:44, 9 September 2015

Uploading Images in 5 Easy Steps  
First Read the help page Images and Copyright Tutorial.
Hint - This exercise is best done by using separate tabs on your browser so that you can keep all the relevant pages easily available. You can also use your own discussion page to copy and paste links, text. PMIDs etc that you will need in this process.
  1. Find an image .
    1. Search PubMed using an appropriate search term. Note that there is a special library of complete (full online) article and review texts called PubMed Central (PMC). Be very careful, while some of these PMC papers allow reuse, not all do and to add the reference link to your image you will still need to use the PMID.
    2. You can also make your own search term. In this link example PMC is searched for images related to "embryo+implantation" http://www.ncbi.nlm.nih.gov/pmc/?term=embryo+implantation&report=imagesdocsum. simply replace "embryo+implantation" with your own search term, but remember not everything in PMC can be reused, you will still need to find the "copyright notice" on the full paper, no notice, no reuse.
    3. Where else can I look? BioMed Central is a separate online database of journals that allow reuse of article content. Also look at the local page Journals that provides additional resources.
    4. You have found an image, go to step 2.
  2. Check the Copyright. I cannot emphasise enough the importance of this second step.
    1. The rule is unless there is an obvious copyright statement that clearly allows reuse (there are several different kinds of copyright, some do not) located in the article or on the article page, move on and find another resource. Not complying with this is a serious academic infringement equivalent to plagiarism."Plagiarism at UNSW is defined as using the words or ideas of others and passing them off as your own." (extract from UNSW statement on Academic Honesty and Plagiarism)
    2. You have found the statement and it allows reuse, go to step 3.
  3. Downloading your image.
    1. Download the image to your own computer. Either use the download image on the page or right click the image.
    2. To find the downloaded image you may have to look in your computer downloads folder, or the default location for downloaded files.
    3. The image file will have its own original name, that you will not be using on the wiki. You can rename it now (see renaming below), but you should also make a note of the original name.
    4. Make sure you have everything ready then for the
    5. You have the image file on your computer, go to step 4.
  4. Uploading your image.
    1. First make sure you have all the information you want to use with the file readily available. There is also a detailed description below.
    2. Towards the bottom of the lefthand menuunder “Toolbox” click Upload file. This will open a new window.
    3. In the top window "Source file", click "Choose file" and then navigate to find the file on the computer. and select the image.
    4. If you have done this correctly the upload window will now have your image file shown in choose file and also in the lower window "File description" in "Destination filename:" DO NOT CLICK UPLOAD FILE YET.
    5. Rename your file in "Destination filename:" this should be a brief filename that describes the image. Not any of the following - the original file name, image, file, my image, your ZID, etc. Many of the common embryology names may have already been used, but you can add a number (01, 02, 03, etc) or the PMID number to the filename to make it unique.
    6. If the filename or image has already been used or exists it will be shown on the upload page. If another student has already uploaded that image you will have to find another file. Duplicated images will not receive a mark, so check before you upload as you cannot delete images.
    7. In the "Summary" window for now just paste the PMID. You will come back and edit this information.
    8. Now click "Upload image" at the bottom of the window, go to step 4.
  5. Edit and Add to your page.
    1. Edit - Open the image with the "Edit" tab at the top of its page. You should see the PMID you had pasted earlier in the new edit window. Add the following information to the summary box.
      1. Image Title as a sub-heading. Under this title add the original figure legend or your own description of the image.
      2. Image Reference sub-sub-heading. Use the PMID link method shown in Lab 1 and you can also have a direct link to the original Journal article.
      3. Image Copyright sub-sub-heading. Add the copyright information under this sub-sub-heading exactly as shown in the original paper.
      4. Student Image template, as shown here {{Template:Student Image}} to show that it is a student uploaded image.
    2. Add - Now add your image to your own page under a subheading for Lab 2 Assessment including a description and a reference link. If still stuck with this last step, look at the example on the Test Student page.
    3. Done!

Students cannot delete images once uploaded. You will need to email me with the full image name and request deletion, that I am happy to do with no penalty if done before I assess.

Non-Table version of this page

Stress Relief....

<html5media height="480" width="640">http://www.youtube.com/watch?v=i9Hwn2DOgKo</html5media>

Interferon regulatory factor-6 and Cleft Lip and Palate

Orofacial clefts such as cleft lip and/or palate are common structural birth defects with birth prevalence ranging from 1/500 to 1/2,000 in different populations. Their complex etiology is not fully understood and both genetic and environmental causes have been established to be involved in cleft lip and/or palate development. Many genes have been found to be involved or correlate with cleft occurrence. One pivotal gene appears to be located on chromosome 1 at the 1q32 region, which encodes interferon regulatory factor-6 (IRF6)[1], an important member of the IRF family involved in oral and maxillofacial development[2]. The failure in growth of the frontonasal prominence, the paired mandibular processes, the paired maxillary processes, and the medial and lateral nasal processes in week 4, together with the failure in fusion of the lateral nasal processes with the maxillary processes, and the medial nasal processes in week 6 and 7 results in orofacial clefting of the upper lip and/or primary palate. Clefts in the secondary palate may arise due to failure in several developmental steps after week 6, such as palatal shelves elevation or migration[3].

Mutations in IRF6 were first identified in patients suffering from Van der Woude syndrome, who often display orofacial clefts in addition to other symptoms. In several subsequent research studies SNPs in IRF6 were also detected in non-syndromic cleft lip and/or palate[4]. The phenotypic heterogeneity of Van der Woude syndrome in comparison to non-syndromic cleft lip and/or palate is hypothesized to be caused by different types of mutations of IRF6 resulting in either a partially or fully nonfunctional protein[5]. In addition, the phenotype might be influenced by the site of mutation[6]. Mutations on a specific sequence variant about ten kb upstream of its transcription start site have been found to keep transcription factor AP-2α from binding and, therefore, influencing IRF6 expression<refname=21331089/>.

There are several hypotheses how IRF6 irregularities may affect development on a molecular level derived from various animal models. IRF6 mutations caused a hyper-proliferative epidermis in mice. This will induce a failure of terminal differentiation in the respective epidermis and generate epithelial adhesions that can clog the oral cavity and create a cleft palate. IRF6 also has been identified as a key determinant of keratinocyte proliferation, oral periderm formation, and its spatio-temporal regulation. p63 activates IRF6 transcription and is....[7]


PMID 19013452 PMID 22931925 PMID 24124047

  1. <pubmed>15185170</pubmed>
  2. <pubmed>23940636</pubmed>
  3. <pubmed>24124047</pubmed>
  4. <pubmed>21331089</pubmed>
  5. <pubmed>22438645</pubmed>
  6. <pubmed>23949966</pubmed>
  7. <pubmed>21331089</pubmed>