Symmetry-out asymmetry-in: the role of DMRT2

Dissertation presented to obtain the PhD degree in Biology

It may come as a surprise that vertebrates are not entirely bilaterally symmetric. In fact, at the internal level they are asymmetric with the organs acquiring a biased disposition along the left-right (LR) axis. Problems in the establishment of both symmetric and asymmetric features may give rise to several human developmental disorders. Thus, it is very important to study in more detail how LR embryonic development is initiated and maintained. The built of the axial skeleton and its associated skeletal muscles is dependent on somite formation and differentiation. The somites are formed as pairs and are bilaterally symmetric between both sides of the LR axis. Interestingly, it has been suggested that asymmetric somite formation may account for problems at the level of the axial skeleton. At the same time that the somites are being formed, asymmetric signals are being transferred only to the left side of the axis being responsible to set up the correct asymmetric internal organs distribution. In fact, an incorrect transfer of information leads to serious problems in organ situs. It has become clear that several mechanisms are necessary to initiate the LR asymmetry pathway however, something that only recently has been acknowledge is that symmetry is not a default state and there are in fact mechanisms responsible for promoting it. It is not completely understood how, but there are indications that there is a crosstalk between the mechanisms necessary to regulate symmetry vs. asymmetry. Surprisingly, a zebrafish transcription factor named Dmrt2a/ Terra, a gene that belongs to a family mainly associated with sex determination, as been shown to play a role in regulating these two contradictory features. Not only is it necessary for bilateral symmetric somite formation but also for the correct establishment of asymmetry in the left side of the axis. Given this, it is extremely important to study the signalling cascade where it operates and to identify its downstream targets.(...)

Apoio financeiro da Fundação para a Ciência e a Tecnologia e do FSE no âmbito do Quadro Comunitário de Apoio, BD nº SFRH/BD/24861/2005