Die Rolle von cDermo-1 und cTwist im Vogelembryo

The aim of this work was to study the regulation and function of the bHLH transcription factors cTwist and cDermo-1. The results obtained may be summarized as follows. <br> <br>1) The induction of cTwist in the paraxial mesoderm of the chick embryo is dependant upon signals emanating from the axial organs. Barrier insertion results in loss of this expression. This effect was rescued by combination of Shh and FGF-8. Furthermore, we could show that the maintenance of the cTwist expression was independent of the inducing signals. Finally BMP-2 is able to downregulate cTwist at early stages while it leads to an upregulation of cTwist later on in development. This indicates an anti-apoptotic function for cTwist in vivo. <br> <br>2) The dermis of the back develops from two separate progenitor populations of the dermomyotome differently regulated by signals from the surrounding structures. The dorsomedial population emanates from the medial lip, where it expresses Wnt-11 and migrates towards the dermis directly overlying the neural tube. This population may be promoted by a Wnt-1 signal from the neural tube as well as an FGF-4 signal, while it is inhibited by Noggin. The dorsolateral progenitor cells deepithelialise out of the central dermomyotome where they express En-1, which is downregulated by BMP, promoting the dermis development in the area directly overlying the somites. These cells also express Wnt-11 and are additionally promoted by an FGF signal. As opposed to the dorsomedial cells however, they are inhibited by Wnt-1. Finally, to support our hypothesis that a downregulation of En-1 in the dorsolateral progenitor population is necessary for dermal differentiation, we retrovirally overexpressed En-1 and showed that this inhibited both dermis and skin appendage development. <br> <br>3) In the development of dermis and skin appendages, we could show that cDermo-1 is essential to induce differentiation of dermal progenitors. Retroviral overexpression of cDermo-1 in the back as well as the limb bud of the chick embryo resulted in the formation of ectopic dermis and skin appendages with respect to the position of the dermis within the embryo. This shows that cDermo-1 is a universal inducer of skin appendages and does not carry a positional information determining the nature of the appendage formed. To further confirm the inducing function of cDermo-1 in dermis development, we downregulated it at earliest developmental stages in both progenitor populations of the back with the help of an ectopic Wnt-4 signal. After reincubation, an inhibition of dermis development and an absence of skin appendages became evident. Finally, we showed that the determining function of cDermo-1 occurred in cells that have already deepithelialised from the somite, and that cDermo-1 had no influence on the process of somite patterning. <br> <br>The aim of future experiments will be to determine the nature of cDermo-1 targets as well as the role played by cell migration in the process of dermal development.

Author dc:creator

• Hornik, Christoph Paul Vincent

Contributors dc:contributor

• Brand-Saberi, Beate

• Dermis

Repository record source_url

https://freidok.uni-freiburg.de/data/1769

OAI identifier oai:identifier

oai:freidok.uni-freiburg.de:1769