Francesc Cebrià Lab

Planarian stem cells, the neoblasts, include truly pluripotent stem cells as well as a number of specialized neoblasts or lineage-committed progenitors from which all cell types differentiate. Thus, they offer an excellent model in which to study stem cell differentiation in vivo. However, very little is known about how pluripotent neoblasts specialize into lineage-committed progenitors and how these progenitors differentiate into their final mature types. In our laboratory we are interested in investigating the molecular and genetic pathways that regulate stem cell differentiation during planarian regeneration and homeostasis.

Contact

fcebrias@ub.edu

+93-4021499

Research

Stem cells maintenance and differentiation

EPIGENETIC REGULATION OF NEOBLAST DIFFERENTIATION

Epigenetic marks such as histone methylation and acetylation regulate the fate of stem cells by maintaining them in an undifferentiated state or triggering cell differentiation when required. However, little is known about the epigenetic regulation of planarian neoblasts. Is this epigenetic regulation conserved in these amazing animals? How does the epigenetic landscape change as neoblasts specialize into lineage-comitted progenitors first and mature cell types later? Our current approach is mainly focussed in understanding the role of the CREB-binding protein (CBP)/p300 family in the regulation of neoblast maintenance and differentiation. Members of this family are multi-functional proteins with histone acetyl-transferase activity that acetylate particular histone residues in order to regulate stem cell and progenitors differentiation in different models. Therefore, planarians offer us a model in which to study the epigenetic regulation of stem cells in vivo.

THE ROLE OF THE EGFR PATHWAY IN NEOBLAST DIFFERENTIATION

Signaling pathways play pivotal roles in triggering proper cell responses to extracellular signals. In the last years we have extensively characterized the function of the epidermal growth factor receptor (EGFR) signalling pathway in neoblast differentiation during planarian regeneration and homesotasis. Our laboratory has identified 10 putative EGF ligands and 6 EGF receptors that are expressed in different cell types. Whereas Smed-egfr-1 and Smed-nrg-1 are required for the final differentiation of gut progenitors into mature gut cells, Smed-egfr-4 seems to be required for the differentiation of eye progenitor into eye cels. These results suggest that in planarians the EGFR pathway could have a general role in the terminal differentiation of the distinct populations of lineage-committed progenitors.

Stem cells (in red) in the mesenchymal space around the gut branches (in green)

Publications

EGFR signaling regulates cell proliferation, differentiation and morphogenesis during planarian regeneration and homeostasis Fraguas, S.; Barberán, S.; Cebrià, F. Developmental Biology 2011. Vol. 354. Pag. 87-101. 10.1016/j.ydbio.2011.03.023. https://www.ncbi.nlm.nih.gov/pubmed/21458439.

Noggin and noggin-like genes control dorsoventral axis regeneration in planarians Molina, M.D.; Neto, A.; Maeso, I.; Gómez-Skarmeta, J.L.; Saló, E.; Cebrià, F. Current Biology 2011. Vol. 21. Pag. 300-305. 10.1016/j.cub.2011.01.016. https://www.ncbi.nlm.nih.gov/pubmed/21295481.

Smed454 dataset: unravelling the transcriptome of Schmidtea mediterranea Abril, J.F.; Cebrià, F.; Rodríguez-Esteban, G.; Horn, T.; Fraguas, S.; Calvo, B.; Bartscherer, K.; Saló, E. BMC Genomics 2010. Vol. 11. Pag. 731. 10.1186/1471-2164-11-731. https://www.ncbi.nlm.nih.gov/pubmed/21194483.

The use of lectins as markers for differentiated secretory cells in planarians Zayas, R.M.; Cebrià, F.; Guo, T.; Feng, J.; Newmark, P.A. Developmental Dynamics 2010. Vol. 239. Pag. 2888-2897. 10.1002/dvdy.22427. https://www.ncbi.nlm.nih.gov/pubmed/20865784.

Gradients in planarian regeneration and homeostasis Adell, T.; Cebrià, F.; Saló, E. Cold Spring Harbor Perspectives in Biology 2010. Vol. 2. Pag. a000505. 10.1101/cshperspect.a000505. https://www.ncbi.nlm.nih.gov/pubmed/20182600.

Expression pattern of the expanded noggin gene family in the planarian Schmidtea mediterranea Molina, M.D.; Saló, E.; Cebrià, F. Gene Expression Patterns 2009. Vol. 9. Pag. 246-253. 10.1016/j.gep.2008.12.008. https://www.ncbi.nlm.nih.gov/pubmed/19174194.

Planarian regeneration: achievements and future directions after 20 years of research Saló, E.; Abril, J.F.; Adell, T.; Cebrià, F.; Eckelt, K.; Fernández-Taboada, E.; Handberg-Thorsager, M.; Iglesias, M.; Molina, M.D.; Rodríguez-Esteban, G. The International Journal of Developmental Biology 2009. Vol. 53. Pag. 1317-1327. 10.1387/ijdb.072414es. https://www.ncbi.nlm.nih.gov/pubmed/19247944.

Organization of the nervous system in the model planarian Schmidtea mediterranea: an immunocytochemical study Cebrià, F. Neuroscience Research 2008. Vol. 61. Pag. 375-384. 10.1016/j.neures.2008.04.005. https://www.ncbi.nlm.nih.gov/pubmed/18499291.

Regenerating the central nervous system: how easy for planarians! Cebrià, F. Development Genes and Evolution 2007. Vol. 217. Pag. 733-748. 10.1007/s00427-007-0188-6. https://www.ncbi.nlm.nih.gov/pubmed/17999079.

Morphogenesis defects are associated with abnormal nervous system regeneration following roboA RNAi in planarians Cebrià, F.; Newmark, P.A. Development 2007. Vol. 134. Pag. 833-837. 10.1242/dev.02794. https://www.ncbi.nlm.nih.gov/pubmed/17251262.

Regeneration and maintenance of the planarian midline is regulated by a slit orthologue Cebrià, F.; Guo, T.; Jopek, J.; Newmark, P.A. Developmental Biology 2007. Vol. 307. Pag. 394-406. 10.1016/j.ydbio.2007.05.006. https://www.ncbi.nlm.nih.gov/pubmed/17553481.

The BMP pathway is essential for re-specification and maintenance of the dorsoventral axis in regenerating and intact planarians Molina, M.D.; Saló, E.; Cebrià, F. Developmental Biology 2007. Vol. 311. Pag. 79-94. 10.1016/j.ydbio.2007.08.019. https://www.ncbi.nlm.nih.gov/pubmed/17905225.

Planarian homologs of netrin and netrin receptor are required for proper regeneration of the central nervous system and the maintenance of nervous system architecture Cebrià, F.; Newmark, P.A. Development 2005. Vol. 132. Pag. 3691-3703. 10.1242/dev.01941. https://www.ncbi.nlm.nih.gov/pubmed/16033796.

Search for the evolutionary origin of a brain: planarian brain characterized by microarray Nakazawa, M.; Cebrià, F.; Mineta, K.; Ikeo, K.; Agata, K.; Gojobori, T. Molecular biology and evolution 2003. Vol. 20. Pag. 784-791. 10.1093/molbev/msg086. https://www.ncbi.nlm.nih.gov/pubmed/12679532.

Origin and evolutionary process of the CNS elucidated by comparative genomics analysis of planarian ESTs Mineta, K.; Nakazawa, M.; Cebrià, F.; Ikeo, K.; Agata, K.; Gojobori, T. Proceedings of the National Academy of Sciences USA 2003. Vol. 100. Pag. 7666-7671. 10.1073/pnas.1332513100. https://www.ncbi.nlm.nih.gov/pubmed/12802012.

Ingestion of bacterially expressed double-stranded RNA inhibits gene expression in planarians Newmark, P.A.; Reddien, P.W.; Cebrià, F.; Sánchez Alvarado, A. Proceedings of the National Academy of Sciences USA 2003. Vol. 100. Pag. 11861-11865. 10.1073/pnas.1834205100. https://www.ncbi.nlm.nih.gov/pubmed/12917490.

FGFR-related gene nou-darake restricts brain tissues to the head region of planarians Cebrià, F.; Kobayashi, C.; Umesono, Y.; Nakazawa, M.; MIneta, K.; Ikeo, K., Gojobori, T.; Itoh, M.; Taira, M.; Sánchez Alvarado, A.; Agata, K. Nature 2002. Vol. 419. Pag. 620-624. 10.1038/nature01042. https://www.ncbi.nlm.nih.gov/pubmed/12374980.

The expression of neural-specific genes reveals the structural and molecular complexity of the planarian central nervous system Cebrià, F.; Kudome, T.; Nakazawa, M.; Mineta, K.; Ikeo, K.; Gojobori, T.; Agata, K. Mechanisms of Development 2002. Vol. 116. Pag. 199-204. https://www.ncbi.nlm.nih.gov/pubmed/12128224.

Dissecting planarian central nervous system regeneration by the expression of neural-specific genes Cebrià, F.; Nakazawa, M.; Mineta, K.; Ikeo, K.; Gojobori, T.; Agata, K. Development Growth and Differentiation 2002. Vol. 44. Pag. 135-146. https://www.ncbi.nlm.nih.gov/pubmed/11940100.

Intercalary muscle cell renewal in planarian pharynx Cebrià, F.; Bueno, D.; Reigada, S.; Romero, R. Development Genes and Evolution 1999. Vol. 209. Pag. 249-253. https://www.ncbi.nlm.nih.gov/pubmed/10079368.