PUBLICATION
Shoc2 controls ERK1/2-driven neural crest development by balancing components of the extracellular matrix
- Authors
- Norcross, R.G., Abdelmoti, L., Rouchka, E.C., Andreeva, K., Tussey, O., Landestoy, D., Galperin, E.
- ID
- ZDB-PUB-221021-10
- Date
- 2022
- Source
- Developmental Biology 492: 156-171 (Journal)
- Registered Authors
- Galperin, Emilia
- Keywords
- ERK1/2, Neural crest, Noonan-like syndrome with loose anagen hair (NSLH), Shoc2, Zebrafish
- Datasets
- GEO:GSE198231
- MeSH Terms
-
- Animals
- Extracellular Matrix
- Humans
- Intracellular Signaling Peptides and Proteins
- MAP Kinase Signaling System/physiology
- Neural Crest
- Noonan Syndrome*/genetics
- Zebrafish/genetics
- PubMed
- 36265687 Full text @ Dev. Biol.
Citation
Norcross, R.G., Abdelmoti, L., Rouchka, E.C., Andreeva, K., Tussey, O., Landestoy, D., Galperin, E. (2022) Shoc2 controls ERK1/2-driven neural crest development by balancing components of the extracellular matrix. Developmental Biology. 492:156-171.
Abstract
The extracellular signal-regulated kinase (ERK1/2) pathway is essential in embryonic development. The scaffold protein Shoc2 is a critical modulator of ERK1/2 signals, and mutations in the shoc2 gene lead to the human developmental disease known as Noonan-like syndrome with loose anagen hair (NSLH). The loss of Shoc2 and the shoc2 NSLH-causing mutations affect the tissues of neural crest (NC) origin. In this study, we utilized the zebrafish model to dissect the role of Shoc2-ERK1/2 signals in the development of NC. These studies established that the loss of Shoc2 significantly altered the expression of transcription factors regulating the specification and differentiation of NC cells. Using comparative transcriptome analysis of NC-derived cells from shoc2 CRISPR/Cas9 mutant larvae, we found that Shoc2-mediated signals regulate gene programs at several levels, including expression of genes coding for the proteins of extracellular matrix (ECM) and ECM regulators. Together, our results demonstrate that Shoc2 is an essential regulator of NC development. This study also indicates that disbalance in the turnover of the ECM may lead to the abnormalities found in NSLH patients.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping