Hematopoietic and neural crest defects in zebrafish shoc2 mutants: A novel vertebrate model for Noonan-like syndrome

Hye In Jang, Erin Oakley, Marie Forbes-Osborne, Melissa V. Kesler, Rebecca Norcross, Ann C. Morris, Emilia Galperin

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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 the Noonan-like syndrome with loose anagen hair. 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 the 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.

Original languageEnglish
Pages (from-to)501-514
Number of pages14
JournalHuman Molecular Genetics
Volume28
Issue number3
DOIs
StatePublished - Feb 1 2019

Bibliographical note

Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press. All rights reserved.

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint

Dive into the research topics of 'Hematopoietic and neural crest defects in zebrafish shoc2 mutants: A novel vertebrate model for Noonan-like syndrome'. Together they form a unique fingerprint.

Cite this