Small molecule developmental screens reveal the logic and timing of vertebrate development. Proc Natl Acad Sci U S A 2000 Nov 21;97(24):12965-9
Date
11/23/2000Pubmed ID
11087852Pubmed Central ID
PMC27161DOI
10.1073/pnas.97.24.12965Scopus ID
2-s2.0-0034700166 (requires institutional sign-in at Scopus site) 463 CitationsAbstract
Much has been learned about vertebrate development by random mutagenesis followed by phenotypic screening and by targeted gene disruption followed by phenotypic analysis in model organisms. Because the timing of many developmental events is critical, it would be useful to have temporal control over modulation of gene function, a luxury frequently not possible with genetic mutants. Here, we demonstrate that small molecules capable of conditional gene product modulation can be identified through developmental screens in zebrafish. We have identified several small molecules that specifically modulate various aspects of vertebrate ontogeny, including development of the central nervous system, the cardiovascular system, the neural crest, and the ear. Several of the small molecules identified allowed us to dissect the logic of melanocyte and otolith development and to identify critical periods for these events. Small molecules identified in this way offer potential to dissect further these and other developmental processes and to identify novel genes involved in vertebrate development.
Author List
Peterson RT, Link BA, Dowling JE, Schreiber SLAuthor
Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCardiovascular System
Central Nervous System
Ear
Embryo, Nonmammalian
Melanocytes
Mutagenesis
Vertebrates
Zebrafish