116
J.-N. Chen and M. C. Fishman
Yost 1996). Molecular cloning of these mutations are underway in the
hope that they will provide further insight into the signaling between the
embryonic axis and the organs.
7.5 Organogenesis Screen
Genetics has been a powerful tool to identify genes and pathways.
Currently many attributes of vertebrate development are extrapolated
from Drosophila. However, this approach is limited when exploring
vertebrate organogenesis, because invertebrate and vertebrate organs are
fundamentally different. For example, Drosophila has an open circulatory system, while vertebrates develop a seamless and closed vasculature. The Drosophila heart is a muscular tube consisting of one major
cell type, the cardiomyocyte. The vertebrate heart consists of multiple
chambers and two major cell types, the inner endocardial cells and the
outer myocardial cells, which also differ between chambers. Therefore,
a vertebrate genome-wide screen focusing on organogenesis is essential
to help understand the formation and function of vertebrate organs.
Nearly 2000 mutations affecting different aspects of zebrafish development have been isolated in two large-scale zebrafish genetic screens,
at Massachusetts General Hospital and at the Max-Plank Institute for
Developmental Biology in Ttibingen (Driever et al. 1996; Haffter et al.
1996). Relatively low numbers of organogenesis mutations were identified in these screens, with the exception of the heart mutants. One likely
explanation is that the heart is placed at a prominent ventral position, but
other organs are placed in a rather deeper layer of the zebrafish embryo.
Therefore, it is more difficult to visualize the visceral organs. The
phenotypes of these mutations can be quite subtle and are easily overlooked. Furthermore, organ development is a relatively late event in
embryogenesis. If genes required for organ development are also required for early events, the organotypic phenotypes will be masked by
early phenotypes. Therefore, it is likely that a simple visual screen is not
optimal when searching for such mutations and specific assays might be
necessary to reveal these mutations. This has proven to be the case by a
recent pilot screen focusing on organogenesis. The design of the pilot
screen is the classic F3 screen for recessive mutations (Haffter et al.
1996). A total of 750 mutagenized genomes were screened using spe-
J.-N. Chen and M. C. Fishman
Yost 1996). Molecular cloning of these mutations are underway in the
hope that they will provide further insight into the signaling between the
embryonic axis and the organs.
7.5 Organogenesis Screen
Genetics has been a powerful tool to identify genes and pathways.
Currently many attributes of vertebrate development are extrapolated
from Drosophila. However, this approach is limited when exploring
vertebrate organogenesis, because invertebrate and vertebrate organs are
fundamentally different. For example, Drosophila has an open circulatory system, while vertebrates develop a seamless and closed vasculature. The Drosophila heart is a muscular tube consisting of one major
cell type, the cardiomyocyte. The vertebrate heart consists of multiple
chambers and two major cell types, the inner endocardial cells and the
outer myocardial cells, which also differ between chambers. Therefore,
a vertebrate genome-wide screen focusing on organogenesis is essential
to help understand the formation and function of vertebrate organs.
Nearly 2000 mutations affecting different aspects of zebrafish development have been isolated in two large-scale zebrafish genetic screens,
at Massachusetts General Hospital and at the Max-Plank Institute for
Developmental Biology in Ttibingen (Driever et al. 1996; Haffter et al.
1996). Relatively low numbers of organogenesis mutations were identified in these screens, with the exception of the heart mutants. One likely
explanation is that the heart is placed at a prominent ventral position, but
other organs are placed in a rather deeper layer of the zebrafish embryo.
Therefore, it is more difficult to visualize the visceral organs. The
phenotypes of these mutations can be quite subtle and are easily overlooked. Furthermore, organ development is a relatively late event in
embryogenesis. If genes required for organ development are also required for early events, the organotypic phenotypes will be masked by
early phenotypes. Therefore, it is likely that a simple visual screen is not
optimal when searching for such mutations and specific assays might be
necessary to reveal these mutations. This has proven to be the case by a
recent pilot screen focusing on organogenesis. The design of the pilot
screen is the classic F3 screen for recessive mutations (Haffter et al.
1996). A total of 750 mutagenized genomes were screened using spe-