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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

11/23/2000

Pubmed ID

11087852

Pubmed Central ID

PMC27161

DOI

10.1073/pnas.97.24.12965

Scopus ID

2-s2.0-0034700166 (requires institutional sign-in at Scopus site)   463 Citations

Abstract

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 SL

Author

Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cardiovascular System
Central Nervous System
Ear
Embryo, Nonmammalian
Melanocytes
Mutagenesis
Vertebrates
Zebrafish