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Antonio Giraldez
Giraldez Lab Website
Antonio Giraldez
Assistant Professor
* Assistant Professor
* B.S. University Autonoma of Madrid (Spain) 1998
* Ph.D. European Molecular Biology Laboratory, Heidelberg (Germany) 2002
Honors:
* EMBO fellow 2002
* HFSP fellow 2003-2006
Research Interests
* Zebrafish Development
* Post-transcriptional regulation by microRNAs
* Gene regulatory networks
* Systems Biology
Current Research:
In our laboratory we use zebrafish as a model system to investigate the role of microRNAs during vertebrate development. We combine genetics, embryology, genomics, chemical and computational biology to address a central question in biology: how does a fertilized egg develop into a complex multicellular embryo. This process requires a precise spatial and temporal regulation of gene expression. MicroRNAs are ~22nt RNA molecules that repress gene expression post-transcriptionaly. More than 4% of the vertebrate genes encode microRNAs that are predicted to regulate more than 25% of the protein coding genes. Thus, microRNAs provide novel regulatory layer of unknown function with potential widespread implications in development and disease. We have generated zebrafish embryos mutant in the microRNA processing machinery (Dicer). Dicer mutants lack all microRNAs and fail to undergo normal gastrulation, brain and muscle morphogenesis.

Two main projects are currently ongoing: 1) We have identified a novel microRNA miR-430 that accelerates the deadenylation of maternal products during embryogenesis to facilitate gastrulation. Interestingly, misexpression of the human homologues (miR-372, miR-17-93) have oncogenic potential. Thus, identification of the in vivo miR-430 targets might provide a fundamental link between development and cancer. 2) MicroRNAs are expressed at the onset of differentiation and continue to be expressed through adulthood. We have observed that miRNAs accelerate target mRNA degradation. Thus, microRNAs targets can be identified by looking at mRNAs upregulated in the absence of the microRNA. We are using microarray analysis in dicer mutant embryos to identify tissue specific microRNA targets in neurons and muscle cells. Computational projects in the lab will analyze the regulatory motifs in microRNAs and 3’UTR elements of their targets to identify the gene networks controlled by microRNAs. Combining in vivo target identification with phenotypic characterization of dicer mutants will help us to understand the function of tissue specific microRNAs during cell fate specification and tissue homeostasis.
Representative Publications:
Choi WY, Giraldez AJ*, Schier AF*. Target Protectors Reveal Dampening and Balancing of Nodal Agonist and Antagonist by miR-430. Science. 2007 Aug 30
* Corresponding Author
Schier AF and Giraldez AJ. MicroRNA function and mechanism, insights from zebrafish. Cold Spring Harb Symp Quant Biol. 2006
Mishima Y#, Giraldez AJ#, Takeda Y, Fujiwara T, Sakamoto H, Schier AF, Inoue, K. Differential regulation of germline mRNAs in soma and germ cells by zebrafish miR-430. Current Biology, 2006 Nov 7;16(21):2135-42. # Equal contribution
Giraldez AJ, et al. Zebrafish miR-430 promotes deadenylation and clearance of maternal mRNAs. Science. 2006. Apr 7;312(5770):75-9.
Giraldez AJ, et al. MicroRNAs regulate brain morphogenesis in zebrafish. Science. 2005 May 6;308(5723):833-8.
Contact Information:
Email: Antonio.Giraldez@yale.edu
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