Title: 1555 - New Zebrafish Models for Human Craniofacial and Skeletal Diseases


Melissa LaBonty, Tufts University
Viktoria Andreeva, Tufts University
Nicholas Pray, Tufts University
Wolfram Goessling, Harvard Medical School
Pamela Yelick (Presenter)
Tufts University


Objectives: Objectives: Our research focuses on mineralized tissue development, homeostasis, disease and regeneration. Craniofacial and skeletal defects are prevalent birth defects, occurring in more than 1/700 live births. Craniofacial and skeletal defects can also result from cancer resections, sports injuries, accidents and battlefield trauma, resulting in significantly reduced quality of life. To address this significant health concern, we use the zebrafish model to perform gene discovery and functional characterizations of molecular signaling pathways regulating normal and syndromic mineralized tissue development. We apply knowledge generated from studies in zebrafish to devise new strategies for the prevention and treatment of human mineralized tissue disease, and to devise more effective tissue engineering strategies for the repair and regeneration of human mineralized craniofacial and skeletal tissues.

Methods: We performed a large-scale, forward genetic, chemical mutagenesis screen in zebrafish to identify early lethal and adult viable mineralized tissue mutants. We used mineralized tissue staining, IHC/IF to characterize each mutant.

Results: We identified a variety of zebrafish mutants as models for human mineralized tissue diseases including: Treacher Collins Syndrome; vertebral disc disease; scoliosis; hemifacial microsomia; midface hypoplasia; osteoporosis; degenerative disc disease; Osteogenesis Imperfecta (OI) and extremity malformations. We are currently performing Next Generation Sequencing to identify candidate alleles, for further validation studies.

Conclusions: We have successfully identified novel zebrafish mutants relevant to a variety of human craniofacial and skeletal diseases. These studies are anticipated to significantly improve our current knowledge and understanding of molecular signaling pathways regulating normal mineralized tissue development and disease, and to provide inroads into new molecular targets and strategies to treat and prevent a variety of human mineralized tissue diseases. These studies were supported by NIH/NIDCR R01DE018043 (PCY) and NIH/NIDCR R21 AR065761 (PCY).

This abstract is based on research that was funded entirely or partially by an outside source:
NIH/NIDCR R01DE018043 (PCY) and NIH/NIDCR R21 AR065761 (PCY).

Disclosure Statement:
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: NONE

Sponsoring Group/Network