PUBLICATION
Hematopoietic and neural crest defects in zebrafish shoc2 mutants: a novel vertebrate model for Noonan-like syndrome
- Authors
- Jang, H., Oakley, E., Forbes-Osborne, M., Kesler, M., Norcross, R., Morris, A.C., Galperin, E.
- ID
- ZDB-PUB-181018-7
- Date
- 2018
- Source
- Human molecular genetics 28(3): 501-514 (Journal)
- Registered Authors
- Galperin, Emilia, Morris, Ann C.
- Keywords
- none
- MeSH Terms
-
- Animals
- Disease Models, Animal
- Germ-Line Mutation
- Hematopoiesis/genetics*
- Intracellular Signaling Peptides and Proteins/genetics*
- Intracellular Signaling Peptides and Proteins/physiology
- Loose Anagen Hair Syndrome/genetics
- MAP Kinase Signaling System/genetics
- MAP Kinase Signaling System/physiology
- Mutation
- Neural Crest/metabolism
- Neural Crest/physiology
- Noonan Syndrome/genetics
- Phenotype
- Zebrafish/genetics
- Zebrafish/physiology
- Zebrafish Proteins/genetics
- PubMed
- 30329053 Full text @ Hum. Mol. Genet.
Citation
Jang, H., Oakley, E., Forbes-Osborne, M., Kesler, M., Norcross, R., Morris, A.C., Galperin, E. (2018) Hematopoietic and neural crest defects in zebrafish shoc2 mutants: a novel vertebrate model for Noonan-like syndrome. Human molecular genetics. 28(3):501-514.
Abstract
The extracellular signal-related kinase 1 and 2 (ERK1/2) pathway is a highly conserved signaling cascade with numerous essential functions in development. The scaffold protein Shoc2 amplifies the activity of the ERK1/2 pathway, and is an essential modulator of a variety of signaling inputs. Germline mutations in Shoc2 are associated with the human developmental disease known as Noonan-like syndrome with loose anagen hair (NSLH). Clinical manifestations of this disease include congenital heart defects, developmental delays, distinctive facial abnormalities, reduced growth and cognitive deficits along with hair anomalies. The many molecular details of pathogenesis of the Noonan-like syndrome and related developmental disorders, cumulatively called RASopathies, remain poorly understood. Mouse knockouts for Shoc2 are embryonic lethal, emphasizing the need for additional animal models to study the role of Shoc2 in embryonic development. Here, we characterize a zebrafish shoc2 mutant, and show that Shoc2 is essential for development, and that its loss is detrimental for the development of the neural crest and for hematopoiesis. The zebrafish model of Noonan-like syndrome described here provides a novel system for the study of structure-function analyses and for genetic screens in a tractable vertebrate system.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping