Shoc2 controls ERK1/2-driven neural crest development by balancing components of the extracellular matrix

• DOI: 10.1101/2022.06.13.495941
• Publication Date: 2022-06-14T11:45:19Z
• Authors: Rebecca G. Norcross; Lina Abdelmoti; Eric C. Rouchka; Kalina Andreeva; Olivia Tussey; Daileen Landestoy; Emilia Galperin
• Keywords: 0301 basic medicine; 03 medical and health sciences; MAP Kinase Signaling System; Neural Crest; Noonan Syndrome; Intracellular Signaling Peptides and Proteins; Loose Anagen Hair Syndrome; Animals; Humans; Zebrafish; Extracellular Matrix

ABSTRACTThe 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.