Biochemistry and Molecular Biology of Development

Summary

The face of vertebrates presents a dazzling array of shapes and sizes, depending largely on the development of the craniofacial skeleton. In particular, cartilage and bones of the face develop from a specific population of neural crest cells. These cells form a series of pharyngeal arches almost identical in all vertebrates. The question then is how these cells are organized in facial features appropriate for each animal? This question is fundamental to understanding not only how diversity is generated faces of vertebrates, but also how they originate in human congenital craniofacial defects affecting development of the face.

In our laboratory we develop two research lines trying to answer questions related to the development of craniofacial structures. The approach is at two levels: the modeling of human craniofacial disorders (cleft palate, aberrations in the formation of maxilla and mandible, etc.) employing the zebrafish as experimental model, and the characterization of molecular mechanisms that control gene expression by involving single-stranded nucleic acid binding proteins.

We use technologies of gain- and loss-of-function of specific proteins (loss of function by microinjection of morpholinos or dominant negative protein overexpression and gain of function by overexpression of wild protein), generation of transgenic fish lines, as well various techniques of developmental biology. In addition, molecular biology techniques, biochemistry and spectroscopy (absorption, fluorescence, and circular dichroism) are usually employed.

As a complementary activity, and derived from knowledge about the biology of zebrafish, in the laboratory it is carried out the DarT test as a fast, simple and highly sensitive and reproducible method to assess water and effluent treatment quality and/or toxicity of synthetic or natural compounds. The test is provided as a service to monitor in water, industrial effluents and sediments, the presence of compounds potentially toxic to humans or the ecosystem.

Research Lines

Modelling human craniofacial pathologies in Zebrafish

The zebrafish has numerous advantages when modelling human diseases. It is a simple model, small, economical, fast-growing and highly fertile. Using this model, we try to explain the molecular basis of human craniofacial disorders which etiology is still not fully understood. We generated a model of Treacher Collins syndrome and identified a group of genes that are currently being studied to establish
their biological roles and molecular relationships. Similarly, we are modelling other human craniofacial disorders to identify and characterize their molecular basis. Craniofacial structures derive primarily from the neural crest, so we try to identify which neural crest marker genes modify their expression during the disease and, what stage of neural

Control of gene expression through molecular folding of guanine quadruplex

The success of embryo development depends on the spatiotemporal control of gene expression, which involves proteins interacting with nucleic acids. Among these, single-stranded nucleic acids binding proteins are versatile actors in the control of gene expression as they may act in different cellular processes. Single-stranded Guanine-rich regions present in DNA or RNA of can fold adopting a tertiary structure named Guanine-quadruplex or G4, which may regulate gene expression. We study CNBP, a protein essential for specification and differentiation of craniofacial structures. CNBP specifically recognizes G-rich single-stranded DNA and, acting as nucleic acid chaperone,
modulates G4 formation in promoter regions of specific genes. Our studies are aimed to the identification of the CNBP cellular targets,
as well as the molecular mechanisms by which this protein performs its biological role.

Selected Publications

  • Weiner AM, Scampoli NL, Calcaterra NB. (2012) Fishing the molecular bases of Treacher Collins syndrome. PLoS One. 2012;7(1):e29574.
  • Weiner,A.M., Sdrigotti,M.A., Kelsh,R.N., and Calcaterra,N.B. (2011). Deciphering the cellular and molecular roles of CNBP during cranial neural crest development. Dev Growth Differ. 2011 Oct;53(8):934-47.
  • Borgognone,M., Armas,P., and Calcaterra,N.B. (2010). Cellular nucleic-acid-binding protein, a transcriptional enhancer of c-Myc, promotes the formation of parallel G-quadruplexes. Biochem. J. 428, 491-498.
  • Calcaterra,N.B., Armas,P., Weiner,A.M., and Borgognone,M. (2010). CNBP: A multifunctional nucleic acid chaperone involved in cell death and proliferation control. IUBMB Life 62, 707-714.
  • Weiner,A.M., Allende,M.L., and Calcaterra,N.B. (2009). Zebrafish cnbp intron1 plays a fundamental role in controlling spatiotemporal gene expression during embryonic development. J. Cell Biochem. 108, 1364-1375.
  • Armas,P., Aguero,T.H., Borgognone,M., Aybar,M.J., and Calcaterra,N.B. (2008a). Dissecting CNBP, a zinc-finger protein required for neural crest development, in its structural and functional domains. J Mol. Biol. 382, 1043-1056.
  • Armas,P., Nasif,S., and Calcaterra,N.B. (2008b). Cellular nucleic acid binding protein binds G-rich single-stranded nucleic acids and may function as a nucleic acid chaperone. J. Cell Biochem. 103, 1013-1036.
  • Weiner,A.M., Allende,M.L., Becker,T.S., and Calcaterra,N.B. (2007). CNBP mediates neural crest cell expansion by controlling cell proliferation and cell survival during rostral head development. J. Cell Biochem. 102, 1553-1570.

Collaborators

  • Miguel Allende; Facultad de Ciencias, Departamento de Biología - Universidad de Chile, Santiago, Chile.
  • Robert Kelsh, Department of Biology & Biochemistry, Universidad de Bath, Reino Unido.
  • María Rita Passos-Bueno, Laboratorio de Genética del Desarrollo Humano, Departamento de Genética y Biología Evolutiva - Instituto de Biociencias, Universidad de San Pablo, Brasil.
  • Flavio Zolessi, Facultad de Ciencias, Universidad de la República, Uruguay.
  • Manuel Aybar, INSIBIO-CONICET, Universidad Nacional de Tucumán, Argentina.

Grants

  • PICT 2007-00648 (IR: Nora Calcaterra). Finalización: 2012.
  • PICT 2007-00738 (IR: Pablo Armas). Finalización: 2011.
  • PIP 00480 (IR: Pablo Armas). Finalización: 2012.
  • Subsidio para actividades de cooperación internacional - Proyecto Conjunto CONICET-Universidad de San Pablo, Brasil.

Director

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Calcaterra, Nora B.
Core CCT
Email: calcaterra@ibr-conicet.gov.ar
Phone: +54 341 4237070
Office Extension: 655
Laboratory Extension: 614

Researchers

Postdoctoral fellows

  • Nadia Scampoli

Doctoral fellows

  • Aldana David
  • Mauco Gil Rosas
  • Ernesto Piga

Undergraduate Students

  • Agustin Lorenzatti
  • Federico Pascutti

Technicians

  • Sebastian Graziati