Zur Rolle der Chorda dorsalis und der Funktion der Dyneine bei der molekularen Rechts-Links-Differenzierung des Säugers
The role of the notochord and the function of dyneins in the molecular left-right-differentiation of mammals
Silke Sabina Schröder
Doctoral thesis
Date of Examination:
2017-06-27
Date of issue:
2017-06-23
Advisor:
Viebahn, Christoph Prof. Dr.
Referee:
Großhans, Jörg Prof. Dr.
Referee:
Mansouri, Ahmed Prof. Dr.
Persistent Address: http://hdl.handle.net/11858/00-1735-0000-0023-3E8A-A
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Abstract
English
Left-right-differentiation is conserved in all vertebrates, also is the orientation of internal organs defined to either the left or the right side and the viscera are rotated in a certain direction. This implicates a conserved mechanism of regulation. Mutations in axonemal dyneins as well the loss of function experiments lead to dysfunctional cilia and a phenotype of situs inversus in human and model organisms, and cilia are said to be critical for the left-right-differentiation in several vertebrates. In rabbits we found long monocilia on the ventral side of the notochord, which are required for the notochordal leftward flow. This structural feature cannot be shown in all animals, e.g. the chick and the pig embryos show a lack of cilia on their early notochord, which is also covered by the endoderm. Notochord and primitive node show great morphologic similarities in chick, pig, rabbit, mouse and human embryos, but we found also functionally important differences concerning the ventral covering of the notochord during the embryonic development. A common structure in all species examined, is the subchordal mesoderm, a mesenchymal structure ventral to the posterior notochord. In addition we studied expression of axonemal dyneins in rabbit and pig embryos. While in the pig the expression in the notochord was not detectable, rabbit embryos reveal a symmetric expression of dynein 5, 9 and 11 in the posterior notochord matching published data in xenopus and suggesting involvement of axonemal dyneins in the left-right symmetry breaking and differentiation. Our data indicates that ciliary flow is not the universal mechanism of left-right symmetry breaking shared by all vertebrates and suggests that another mechanism has to be postulated presuming a conserved regulatory mechanism of left-right-differentiation and symmetry breaking.
Keywords: notochord; rabbit; mammal; embryo; left-right-differentiation; subchordal mesoderm; development; gastrulation; ciliary flow; axonemal dynein; symmetry breaking
Schlagwörter: Chorda dorsalis; Kaninchen; Säuger; Embryo; Rechts-Links-Differenzierung; subchordales Mesoderm; Entwicklung; axonemale Dyneine; Symmetriebrechung; Gastrulation
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Human- und Zahnmedizin [2333]