Dr. Katherine Fantauzzo (right) and her former graduate student, Dr. Brenna Dennison, University of Colorado Anschutz Medical Campus (USA)

Formation of Facial Structures: Using Light Microscopy to Study the Causes of Facial Clefting

Craniofacial development is a complex morphogenetic process that requires a precise interplay of multiple cell and tissue types to generate the frontonasal skeleton. Disruption of this process results in highly prevalent human birth defects such as cleft lip and palate.

Dr. Katherine Fantauzzo is an Assistant Professor in the Department of Craniofacial Biology at the University of Colorado Anschutz Medical Campus (USA). Her research uses mouse embryos to provide insight into the mechanisms underlying mammalian craniofacial development and new therapeutic directions for the treatment of human craniofacial birth defects.

Her recent work with her former graduate student, Dr. Brenna Dennison, was published in Development. Their image of the cranial neural folds and first pharyngeal arches of a mouse embryo acquired with a ZEISS Axio Observer 7 microscope with Apotome was featured on the journal cover.

We spoke with her to learn more about her research and use of microscopy.

Mouse embryonic cranial neural folds and first pharyngeal arches imaged with ZEISS Axio Observer 7 with structured illumination featured on the cover of

The work of Drs. Dennison and Fantauzzo featured on the cover of Development. Image acquired using ZEISS Axio Observer 7 microscope with Apotome.

Tell us more about your area of research.

Our laboratory investigates the mechanism and function of signaling through a particular family of receptor tyrosine kinases, the platelet-derived growth factor receptor (PDGFR) family, in development of the mouse craniofacial skeleton. Our goal is to characterize novel intracellular pathways and cellular processes engaged downstream of PDGFR induction.

Mutations in the genes encoding human PDGFRs cause non-syndromic cleft lip and palate as well as syndromes characterized by facial dysmorphism. Defects in craniofacial development, including cleft lip and palate, comprise one of the most prevalent birth defects in humans. By identifying the mechanisms by which PDGFRs regulate gene expression and cell activity, our findings have the potential to provide new therapeutic directions for the treatment of human craniofacial birth defects.

What scientific advances did you publish in your recent article?

We found that PDGFRalpha signaling regulates the expression of genes involved in palatal shelf morphogenesis through alternative RNA splicing and identified phosphorylation of RNA-binding proteins downstream of this pathway as a mechanism that contributes to this response. Our findings further revealed that the RNA-binding protein Srsf3 is a critical regulator of craniofacial development in the mouse, as embryos with ablation of Srsf3 exhibit midline facial clefting. These results highlighted a novel, and surprising, role for PDGFR signaling in regulating RNA processing.

How do you use microscopy in your research?

We use microscopy to dissect mouse embryos and image these embryos as well as particular craniofacial tissues and individual cells. We do this using both brightfield and fluorescence microscopy.

In our recent publication, we used microscopy to assess the expression of Srsf3 during development and to determine the craniofacial phenotypes of mouse embryos upon Srsf3 ablation. Using our ZEISS Axio Observer 7 microscope, we are able to image the craniofacial region of mid-gestation mouse embryos in a single field of view at very high resolution.

Sox10-positive neural crest cells (magenta) as detected by immunofluorescence staining of a section of cranial neural folds from an E8.0 mouse embryo. Nuclei were stained with DAPI (blue). Imaged with ZEISS Axio Observer 7 fluorescence microscope with structured illumination. Courtesy: Dr. Katherine Fantauzzo, University of Colorado Anschutz Medical Campus (USA)

Sox10-positive neural crest cells (magenta) as detected by immunofluorescence staining of a section of cranial neural folds from an E8.0 mouse embryo. Nuclei were stained with DAPI (blue). Imaged with ZEISS Axio Observer 7 with Apotome.

Read Dr. Dennison and Dr. Fantauzzo’s article in Development or learn more about the Fantauzzo lab and their beautiful microscopy images here.

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