Symmetry & Development

Research Interests

Our group is studying the molecular mechanisms that control asymmetric versus symmetric development, using the chick and the zebrafish embryos as model organisms. During embryonic development it is important to create left-right asymmetry in the lateral plate mesoderm to allow the correct positioning of the internal organs. In addition, it is fundamental to maintain symmetry between the left and the right sides of the presomitic mesoderm to ensure the perfect allocation of symmetric body structures such as the axial skeleton, skeletal muscles and peripheral nerves.

Group Members

Rita Fior	Postdoc
	Tel: 21 446 4632
Sofia Rodrigues	Postdoc
	Tel: 21 446 4632
Susana Pascoal	Postdoc
	Tel: 21 446 4632
Raquel Mendes	Research Technician
	Tel: 21 446 4632
Isabel Palmeirim	Visitor
	Tel: 21 446 4632

Research Project

Left-right synchronization of the segmentation clock

The bilateral symmetry of the adult vertebrate body is evident at the level of the axial skeleton and the skeletal muscles. These structures derive from the somites. The formation of the somites is under the control of a molecular clock, revealed by the cyclic presomitic mesoderm expression of components of the Notch and Wnt signalling pathways. We have recently shown that in the absence of the transcription factor Terra, the onset of the segmentation clock is desynchronized between the left and the right presomitic mesoderm precursors. This implies that somite formation is not a bilaterally symmetrical process by default: rather its symmetry needs to be actively maintained by a mechanism that involves Terra and the recently implicated retinoic acid signalling. In addition, we have also shown that without Terra the embryos display a randomized expression of left-right markers in the lateral plate mesoderm, with a subsequent randomization of heart position. These studies have lead to the identification of the first molecular coordinator of two processes that are important to set up the vertebrate body plan: left-right asymmetry and presomitic mesoderm bilateral symmetry. We are studying the mechanism of Terra action using the zebrafish and the chick as model systems.

Research Project

Molecular basis of medio-lateral presomitic specification

The discovery that segmentation and somite formation is a process guided by Medial-PSM raises the question: What are the genes responsible for the segmentation autonomy of Medial-PSM? To address this problem, we have performed a subtraction screening of cDNA libraries from Medial versus Lateral chick PSM in order to determine the genes differentially expressed in Medial-PSM. We have already done a first round screening and one new gene (clone 43) was selected for study based upon its differential pattern of expression in the Medial-PSM using whole-mount/cross section in situ hybridisation techniques. The role of clone 43 and other selected Medial-PSM genes in establishing the segmentation autonomy will be analysed by gain and loss-of-function experiments using in ovo electroporation, soaked beads, transfected COS cells, virus RCAS and RNA interference. Additionally, from the first round screening, two new genes (clone 28 and clone 45) were selected based on their specific pattern of expression in anterior PSM and their absolute complementary expression to the secreted factor fgf8. These genes are therefore good candidates for the establishment of the maturation territory in anterior PSM.

Funding

POCTI/BCI/45914/2002
Molecular and cellular characterisation of segmentation in the chick embryo.

Collaborators

Escola de Ciências da Saúde, Instituto em Ciências da Vida e da Saúde, Universidade do Minho, Braga
Isabel Palmeirim

Publications

Saúde, L., Lourenço, R., Gonçalves, A. and Palmeirim, I. (2005). terra is a left-right asymmetry gene required for left-right synchronization of the segmentation clock Nature Cell Biology 7(9) :918-20

Freitas, C., Rodrigues S., Saúde, L. and Palmeirim, I. (2005). Running after the clock The International Journal of Developmental Biology 49(2-3) :317-2

Coutinho, P., Parsons, M. J., Thomas, K. A., 1, Hirst, E. M. A., Saúde, L., Campos, I., Williams, P. H. and Stemple, D. L. (2004). Differential requirements for COPI transport during vertebrate early development. Developmental Cell 7(4) :547-58

Feldman, B., Concha M. L., Saúde, L., Parsons, M. J., Adams, R. J., Wilson, S. W. and Stemple, D. L. (2002). Lefty antagonism of Squint is essential for normal gastrulation. Current Biology 12 (24) :2129-35

Parsons, M. J., Pollard, S. M., Saúde, L., Feldman, B., Coutinho, P., Hirst, E. M. and Stemple, D. L. (2002). Zebrafish mutants identify an essential role for laminins in notochord formation Development 129(13) :3137-46

Saúde, L., Woolley, K., Martin, P., Driever, W. and Stemple, D. L. (2000). Axis-inducing activities and cell fates of the zebrafish organizer. Development 127(16) :3407-17

Heisenberg, C-P., Tada, M., Rauch, G-J., Saúde, L., Concha, M. L., Geisler, R., Stemple, D. L., Smith, J. C. and Wilson, S. W. (2000). Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. Nature 405 :(6782)76-81