Matthew Harris, Ph.D.

no image
Matthew Harris, Ph.D.
Children's Hospital Boston
Enders 260.2
300 Longwood Ave
Boston, MA 02115
(617) 919-2032

The Harris laboratory is interested in the control of growth and proportion in the development of the skeleton.   The lab uses the zebrafish as a model system to probe the genetic basis of this control.

 

 

Postembryonic development: on growth and form

Our work centers on uncovering the genes that control development of the skeleton after embryogenesis is completed, often referred to as post-embryonic development.  Post-embryonic development is where coordinated growth and differentiation of tissues and organs lead to the manifestation of form and function in the adult.  Many mutations that effect gene function during early development are lethal. Variation in gene function during postembryonic development will be less likely to result in lethality.  Thus, these particular types of changes are more likely to be associated with observed changes in adult form and physiology, both in natural variation and disease.   We are particularly interested in the genetic regulation of proportional growth and timing during development.  We focus on the development of the skeleton of the fins and skull of the zebrafish and have isolated novel mechanisms regulating growth and differentiation.

Fish as genetic models for understanding the development of the skeleton and the generation of adult form.

Fish provide a unique system in which to address this question.  First, the zebrafish is an excellent genetic model, allowing for unbiased screens in a vertebrate for novel regulators of bone development.  Additionally, the external development and transparency of the zebrafish permits real-time visualization of skeletal development.  The conservation of gene function among vertebrates allows an extension of findings in zebrafish to mammals and provides non-mammalian genetic models for human skeletal disease.

Comparative genetics: why diversity counts

Teleost fish are the most diverse assemblage of vertebrates, with over 28,000 species.  This diversity permits an analysis of how genes are differentially regulated to control growth and differentiation.  An example of a research model that is currently used by the lab is that of the medaka fish.  Medaka and zebrafish share a common ancestor about 135 million years ago (roughly comparable to the divergence between mouse and man).  While they share a similar background, these fish have a unique evolutionary history that has led to changes in gene function.   We have already shown that a comparison of gene function in these two teleosts can uncover mechanisms of gene function underlying skeletal diversity (Rohner et al 2009).   We are currently using this model as a complement to the zebrafish as a genetic model for skeletal biology research.

About Matthew Harris

Dr. Harris studied Marine Science at Boston University at the Marine Biological Laboratories in Woods Hole.  He received his doctorate in Cell and Molecular Biology at the University of Wisconsin-Madison, working in the lab of John Fallon on the Evolution and Development of avian skin appendages.  Further postdoctoral work was done in the Nuesslein-Volhard laboratory at the Max Planck Institute for Developmental Biology in Tuebingen, Germany.  There, he initiated work looking at the genetic control of postembryonic development in the zebrafish and how changes in this developmental period influence/bias the generation of morphological diversity.