Genetic analysis of the development of adult structures

While previous large scale genetic screens defined genes necessary for embryogenesis, the genetic basis of post-embryonic development leading to the adult morphs is not well known.   Natural selection during evolution specifically acts on variations in the adult form.  Variation in adult morphology permits differentiation among species much more than the embryonic structures and distinguish even closely related fish.   However, we know very little concerning the genes controlling the formation and variaiton of adult morphology.
 
In order to understand the genetic basis for the development of adult structures, we have participated in the large-scale mutagenesis screen and isolated mutants affected in the formation of adult structures of the exoskeleton (fins and scales) and the skull. Many such organs are composed of dermal bones that arise during juvenile development in close association with the integument.  We isolated a wide array of mutants affected in the shape of the skull, scalation, and the size and structure of fins. 

Our work is focused on two topics:

• Developmental and genetic basis of scale development in zebrafish and loss in natural cypriniforme fish populations
  
• Developmental and genetic control of organ growth and size control:
• Fins as a model system to examine genetic control of growth.
• Genetic analysis of skull development and the integration of growth and form
  

The phenotype common to mutations in two genes, finless and Nackt, shares the absence of scales, fin rays and teeth.  A second mutant, spiegel, lacks only parts of the scales and resembles in appearance the mirror carp, a domesticated variety with strongly reduced scales.  Additionally, many other naturally occurring species of fish have lost scales independently during teleost evolution.  We are comparing variation at gene loci in scaleless fish species with closely related species that have retained scales to assess if scale loss in evolution is caused by alterations in any of the genes we identified in the zebrafish.

               


Our data demonstrate the potential of the adult screen in isolating mutations in genes specifically required for the development of adult structures as well as those (as hypomorphic alleles) that have a vital function already early in development. We speculate that the genes defined by the forward mutagenic approach in the adult screen will be associated with changes in adult form in evolution and in human disease.

Additionally, as a means to understand the developmental basis of coordinated changes in dermal bone structures, we are investigating the role of the neural crest in the formation and variation of adult structure.

Personnel:

• Dr. Matthew Harris                                          Postdoc (04/03 – present)

• Nicolas Rohner                                               PhD student (07/05 – present)

• Peter Konstantinidis                                       PhD student (07/06 – 12/06)

• Iris Koch                                                            Technician

Collaborators:

• Dr. Heinz Schwarz                                            Electron Microscopy Unit, MPI EB   
  
• Dr. Laszlo Orban                                               Temasek Life Sciences Laboratory, Singapore
• Dr. Miklós Bercsényi                                         University of Pannonia, Keszthely, Hungary