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Academic Degrees

• 2006, "Agregação" (D.Sc.) degree in Biotechnology, at University of Algarve.

• 1998, Ph.D. degree in Biomedical Sciences by the Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Porto, Portugal. The research work was conducted under the supervision of Prof. Edward M. De Robertis, at the Department of Biological Chemistry, University of California School of Medicine, Los Angeles (UCLA).

• 1993, B.Sc. in Biology by the University of Coimbra, Portugal.

Positions

• 2007-Present – External Group/PI at Instituto Gulbenkian de Ciência, Oeiras, Portugal.

• 2003-Present – Associate Professor at University of Algarve.

• 1999-2003– Assistant Professor at University of Algarve.

• 1999-2006 - I.G.C. Member, Principal Investigator. Head of the Early Mouse Development Laboratory at Instituto Gulbenkian de Ciência, Oeiras, Portugal.

• 1998-1999 - HHMI Associate. Postdoctoral position at the Howard Hughes Medical Institute, at the University of California Los Angeles.

• 1994-1998 - Visiting Scientist/Staff Research Associated under the supervision of Prof. Edward M. De Robertis, at the Department of Biological Chemistry, University of California School of Medicine, Los Angeles.

• 1993-1994 - First year PhD. student of the Programa Gulbenkian de Doutoramento em Biologia e Medicina (PGDBM, see Appendix 1), at the Instituto Gulbenkian de Ciência (IGC), Oeiras, Portugal.

• 1992-1993 - Teaching Assistant (TA, or “monitor”) of Molecular Genetics at Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Porto, Portugal.

Research Interests

Dr. Belo' research at CBME is centered in the establishment of the body axis of the early vertebrate embryo. Which are the genes and processes involved in the induction and formation of the heart, and of the forebrain and associated process of anterior neural induction. Generation and study of mouse models of human genetic diseases. For this purpose, we use the mouse, Xenopus and chick embryos as model systems using the most up to date technologies in molecular embryology. Those include generation and analysis of KO and transgenic mouse lines, microinjection into Xenopus embryos and chick electroporation.

Mechanisms of head induction in vertebrates:

The Xenopus cerberus gene encodes a secreted factor expressed in the Spemann organizer that induces ectopic head formation when its mRNA is injected into Xenopus embryos. We reported the isolation of the related mouse cerberus-like ( cer-l ), a gene encoding a novel secreted protein that is specifically expressed in the Anterior Visceral Endoderm (AVE) and mesendoderm that underlies the presumptive anterior neural plate. The specific aim of our research is to further contribute to the understanding of the role of the anterior visceral endoderm and the Cerberus/Dan family of secreted factors in the specification of vertebrate  embryonic structures.

We have genetically inactivated by homologous recombination in ES Cells the cer-l gene. Currently we are studying possible genetic interactions of cer-l with these other genes involved in head formation to try to find the compensatory pathways involved in this process.

Using a differential screening approach, we are on the way to try to isolate novel genes expressed in the Anterior Visceral Endoderm. For this end we have generated a transgenic mouse line expressing EGFP under the control of the mCer-l promoter . In this transgenic line the A-P axis reorientation could be followed, by the fluorescently labelled AVE cells, even before gastrulation. This allowed us perform a gene expression profiling of both Anterior and Posterior regions using GeneChips ® (Affymetrix ®) identified several new transcripts expressed at the very early stages of A-P axis establishment.

Using the vertebrate embryo, we are currently studying the regulatory genomic regions of the Cerberus-like gene family. We hope to gain further insight into the mechanism by which cerberus is required controlled inactivation of specific signaling molecules in the anterior endoderm of the vertebrate embryo. To investigate the extent of evolutionary conservation between the regulatory sequences of mouse, Xenopus and chick cer-like genes, intra and cross species promoter studies are being performed.

Mechanisms of Left/Right asymmetry in vertebrates:

Correct establishment of the L/R body asymmetry in the mouse embryo requires asymmetric activation of the evolutionary conserved Nodal signaling cascade in the L-LPM. By sequence homology analysis, we have identified a novel mouse gene of the Cerberus-like family, that we designated cerberus-like 2 ( cerl-2 ). We have characterized the function of cerl-2 , a novel Nodal antagonist, which displays a unique asymmetric expression on the right side of the mouse node. cerl-2 knock-out mice display multiple laterality defects including randomization of L/R axis. Strikingly, these defects can be partially rescued by removing one nodal allele. Our results demonstrate that Cerl-2 plays a key role restricting the Nodal signaling pathway towards the left side of the mouse embryo by preventing its activity in the right side.

For more information: The JBELO Group at IGC

Projects Grants

POCTI/BCI/46392/2002 - "O papel multifunctional da endomesoderme anterior no processo da formação da cabeça em vertebrados".

POCTI/NSE/46420/2002 - "Regulação intracellular durante o desenvolvimento do cérebro, da via de sinal FGF8 pela fosfatase MKP3".

POCTI/CBO/46691/2002  - "Identification and transcriptome functional analysis of heart/hemangioblast commun precursor cellsin the chick embryo".

GRICES/CNR/4.1.1/03- "Identification and characterization of genetic interactions between members of nodal pathway by double mutant mouse analysis".  

Project co-leader

POCTI/MGI/32513/99 - "Fungal and mouse models of human mitochondrial disease".

POCTI/CBO/39099/01 - "Structure and function of the centrosomal proteins HsMob".

POCTI/BME/46257/02 - "Vertebrate left/right asymmetry: analysis of the transcriptional regulation of chick Caronte during embryonic development".

Collaborator

POCI/BIO/62476/2004 - “Viral Nanoparticles for Molecular and Gene Therapy”.

POCTI/ BIA-BCM/58677 /2004 - "Spatial-temporal pattern of expression and regulation of Matrix Gla Protein (MGP) during early development in X. laevis".

Selected Publications (2006 - 2010)

Oki, S., Kitajima, K., Marques, S., Belo, J.A., Yokoyama, T., Hamada, H., Meno, C. (2009) "Reversal of left-right asymmetry induced by aberrant Nodal signaling in the node of mouse embryos", Development, 136(23):3917-3925.

 J. A. Belo, Ana C. Silva, Ana C. Borges, Mário Filipe, Margaret Bento, Lisa Gonçalves, Marta Vitorino, Ana M. Salgueiro, Vera Texeira, Ana T. Tavares & Sara Marques (2008). Generating asymmetries in the early vertebrate embryo: the role of the Cerberus-like family. (in press, IJDB DOI: 10.1387/ijdb.072297jb).

Giovanna L. Liguori*, Ana C. Borges*, Daniela D’Andrea, Annamaria Liguoro, Lisa Gonçalves, Ana M. Salgueiro, M. Graziella Persico & J. A. Belo (2008). Cripto-independent nodal signalling promotes positioning of the A-P axis in the early mouse embryo. Developmental Biology, 315(2):280-289 (* equal authors).

Costa, MJL.; Pedro, L.; Alves de Matos, A.P.; Aires-Barros, M.R.; Belo, J.A.; Gonçalves, J.; Ferreira, G.N.M. (2007) "Molecular construction of Bionanoparticles: Chimeric Simian Immunodeficiency - Human Immunodeficiency nanoparticles with minimal viral protein content.” , Biotechnology and Applied Biochemistry, 48: 35-43.

J. A. Belo, Margaret C. Bento, Ana T. Tavares (2007) "Functional analysis of novel genes differentially expressed genes in heart/hemangioblast precursor cells (H/HPC)",  ABSTRACTS / Developmental Biology 306, 396–410.

Ana T. Tavares, Sofia Andrade, Ana C. Silva & José A. Belo (2007). Cerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick embryo. Development 134(11): 2051-2060.

A. C. Silva, M. Filipe, M. Vitorino, H. Steinbeisser and José A. Belo (2006). Developmental Expression of Shisa-2 in Xenopus laevis . IJDB 50, 575-579.

M. Filipe, L. Gonçalves, M. Bento, A. C. Silva and José A. Belo (2006). Comparative expression of mouse and chicken Shisa homologues during early development. Dev. Dyn. 235(9), 2567-73.

A. M. Salgueiro, M. Filipe & José A. Belo (2006). Expression of N- acetylgalactosamine 4-sulfate 6 -O- sulfotransferase during early mouse embryonic development . IJDB 50: 705-708.

Echevarria, D., Martínez, S., Marques, S., Lucas-Teixeira, V. & Belo, J.A. (2005). Mkp3 is a negative feedback modulator of Fgf8 signaling in the mammalian isthmic organizer. Dev. Biology 277 (1), 114-128.

Chiharu Kimura-Yoshida, Hiroshi Nakano, Daiji Okamura, Kazuki Nakao, Shigenobu Yonemura, José A. Belo , Shinichi Aizawa, Yasuhisa Matsui and Isao Matsuo (2005). Canonical Wnt signaling and its antagonist regulate anterior-posterior axis polarization by guiding cell migration in mouse visceral endoderm. Dev. Cell . 9, 639-650.

Natércia Conceição*, A.C. Silva*, João Fidalgo, José A. Belo, M. Leonor Cancela (2005). Identification of alternative promoter usage for Matrix Gla Protein gene: evidence for differential expression during early development in Xenopus laevis . FEBS Journal 272, 1501-1510. (* equal authors).

Diego Echevarria, José António Belo and Salvador Martínez (2005). Modulation of Fgf8 activity during vertebrate brain development. Brain Research Reviews 49, 150-157.

Mesnard, D.*, Filipe, M.*, Belo, J.A. & Zernicka-Goetz, M. .(2004). Emergence of the anterior-posterior axis after implantation relates to the re-orienting symmetry of the mouse embryo rather than the uterine axis. Current Biology 14, 184-196. (* equal authors).

Marques, S., Borges, A.C., Silva, A.C., Freitas, S., Cordenonsi, M. & Belo J.A. (2004). The activity of the Nodal antagonist Cerl-2 in the mouse node is required for correct L/R body axis. Genes & Dev. 18, 2342-2347.

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