Where Ideas Grow

Vertebrate Development and Regeneration

ABOUT

The Vertebrate Development and Regeneration group studies the mechanisms of cis-transcriptional regulation of genes and how mutations on non-coding cis-transcriptional regulatory sequences might impact in the development of some human diseases, in particular diabetes and pancreatic cancer. We employ genomic strategies to identify non-coding cis-transcriptional regulatory sequences and we perform genetic functional assays in zebrafish to evaluate the function of these sequences.

 

RESEARCH

Defining when, where and how much genes are transcriptionally expressed is one of the major mechanisms that control organogenesis and organ function. Variations in these mechanisms might contribute to disease. The transcriptional regulation of genes is achieved by non-coding cis-regulatory elements (CREs) spread over large genomic distances and is important for the proper development, function and homeostasis of organs. Our major research interest is to understand these mechanisms of transcriptional regulation. We use the zebrafish as a vertebrate model and we focus in the pancreas, our organ of choice.
Over the last years, we have developed methods to detect, validate and disrupt CREs. Among these tools, we have developed the Zebrafish Enhancer Detection vector, that contains an in vivo reporter to test cis-regulatory activity of sequences. We have also developed the Expression Disruption vector, that allows to disconnect CREs from their target genes. Combining these tools with genome wide approaches such as Assay for Transposase-Accessible Chromatin, Chromatin Immunoprecipitation and Circularized Chromosome Conformation Capture, we are uncovering CREs active in the pancreas and we are accessing their biological function by disturbing their activity. This information will be extremely relevant to clarify the role of CREs in the development of two major pancreatic diseases Diabetes and Pancreatic Cancer.

Zebrafish in vivo reporter line for insulin (GFP; green) and somatostatin (mCherry; red) expression

Team

Selected Publications

Bordeira-Carriço R., Teixeira J., Duque M., Galhardo M., Ribeiro D., Acemel R.D., Firbas P.N., Tena J.J., Eufrásio A., Marques J., Ferreira F.J., Freitas T., Carneiro F., Goméz-Skarmeta J.L., Bessa J.,
Multidimensional chromatin profiling of zebrafish pancreas to uncover and investigate disease-relevant enhancers. Nature Communications13(1):, 2022. [Journal: Article] [IF: 14,9 (*)]
DOI: 10.1038/s41467-022-29551-7 SCOPUS: 85128076921

Sousa F., Costa-Pereira A.I., Cruz A., Ferreira F.J., Gouveia M., Bessa J., Sarmento B., Travasso R.D.M., Mendes Pinto I.,
Intratumoral VEGF nanotrapper reduces gliobastoma vascularization and tumor cell mass. Journal of Controlled Release339:381-390, 2021. [Journal: Article] [CI: 1] [IF: 9,8 (*)]
DOI: 10.1016/j.jconrel.2021.09.031 SCOPUS: 85116870935

Duque M., Amorim J.P., Bessa J.,
Ptf1a function and transcriptional cis-regulation, a cornerstone in vertebrate pancreas development. FEBS Journal:, 2021. [Journal: Review] [CI: 1] [IF: 5,5 (*)]
DOI: 10.1111/febs.16075 SCOPUS: 85108873510

Ferreira F.J., Carvalho L., Logarinho E., Bessa J.,
Foxm1 modulates cell non-autonomous response in zebrafish skeletal muscle homeostasis. Cells10(5):, 2021. [Journal: Article] [CI: 1] [IF: 6,6 (*)]
DOI: 10.3390/cells10051241 SCOPUS: 85107456993

Vaz S., Ferreira F.J., Macedo J.C., Leor G., Ben-David U., Bessa J., Logarinho E.,
FOXM1 repression increases mitotic death upon antimitotic chemotherapy through BMF upregulation. Cell Death and Disease12(6):, 2021. [Journal: Article] [CI: 1] [IF: 8,5 (*)]
DOI: 10.1038/s41419-021-03822-5 SCOPUS: 85106857863

Amorim J.P., Bordeira-Carriço R., Gali-Macedo A., Perrod C., Bessa J.,
CRISPR-Cas9-Mediated Genomic Deletions Protocol in Zebrafish. STAR Protocols1(3):, 2020. [Journal: Article]
DOI: 10.1016/j.xpro.2020.100208 SCOPUS: 85108300986

Silva M.C., Fernandes Â., Oliveira M., Resende C., Correia A., de-Freitas-Junior J.C., Lavelle A., Andrade-Da-Costa J., Leander M., Xavier-Ferreira H., Bessa J., Pereira C., Henrique R.M., Carneiro F., Dinis-Ribeiro M., Marcos-Pinto R., Lima M., Lepenies B., Sokol H., Machado J.C., Vilanova M., Pinho S.S.,
Glycans as immune checkpoints: Removal of branched N-glycans enhances immune recognition preventing cancer progression. Cancer Immunology Research8(11):1407-1425, 2020. [Journal: Article] [CI: 7] [IF: 11,2]
DOI: 10.1158/2326-6066.CIR-20-0264 SCOPUS: 85100138005

Castro A.F., Loureiro J.R., Bessa J., Silveira I.,
Antisense transcription across nucleotide repeat expansions in neurodegenerative and neuromuscular diseases: Progress and mysteries. Genes11(12):1-30, 2020. [Journal: Review] [CI: 4] [IF: 4,1]
DOI: 10.3390/genes11121418 SCOPUS: 85097037527

Eufrásio A., Perrod C., Ferreira F.J., Duque M., Galhardo M., Bessa J.,
In vivo reporter assays uncover changes in enhancer activity caused by type 2 diabetes–associated single nucleotide polymorphisms. Diabetes69(12):2794-2805, 2020. [Journal: Article] [CI: 2] [IF: 9,5]
DOI: 10.2337/db19-1049 SCOPUS: 85096579124

Amorim J.P., Gali-Macedo A., Marcelino H., Bordeira-Carriço R., Naranjo S., Rivero-Gil S., Teixeira J., Galhardo M., Marques J., Bessa J.,
A Conserved Notochord Enhancer Controls Pancreas Development in Vertebrates. Cell Reports32(1):, 2020. [Journal: Article] [CI: 2] [IF: 9,4]
DOI: 10.1016/j.celrep.2020.107862 SCOPUS: 85087427741

Seixas A.I., Loureiro J.R., Costa C., Ordóñez-Ugalde A., Marcelino H., Oliveira C.L., Loureiro J.L., Dhingra A., Brandão E., Cruz V.T., Timóteo A., Quintáns B., Rouleau G.A., Rizzu P., Carracedo Á., Bessa J., Heutink P., Sequeiros J., Sobrido M.J., Coutinho P., Silveira I.,
A Pentanucleotide ATTTC Repeat Insertion in the Non-coding Region of DAB1, Mapping to SCA37, Causes Spinocerebellar Ataxia. American Journal of Human Genetics101(1):87-103, 2017. [Journal: Article] [CI: 58] [IF: 8,9]
DOI: 10.1016/j.ajhg.2017.06.007 SCOPUS: 85021415706

Fernández-Miñán A., Bessa J., Tena J.J., Gómez-Skarmeta J.L.,
Assay for transposase-accessible chromatin and circularized chromosome conformation capture, two methods to explore the regulatory landscapes of genes in zebrafish. Methods in Cell Biology135:413-430, 2016. [Book Series: Article] [CI: 16] [IF: 1,3]
DOI: 10.1016/bs.mcb.2016.02.008 SCOPUS: 84961124971