16 Nov Signaling Pathways Critical to Facial Development, and Birth Defects Identified
MedicalResearch.com Interview with:
Philippe M Soriano, PhD
Professor, Cell, Developmental & Regenerative Biology and
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study?
Response: The study was performed primarily to help understand how signals sent from growth factors to their receptors on the cell surface (see reply to the following question) initiate a cascade of events within the cells that lead to proliferation, survival, or other biological responses. This is important to know because deregulation of many of these pathways can lead to cancers.
MedicalResearch.com: Would you explain what is meant by FGFs and their interaction with RTKs?
Response: FGFs are cell signaling proteins that are also known as growth factors because they often lead to cell proliferation. They act by binding to receptors on the cell surface that are part of a family of receptor tyrosine kinases (RTKs). These RTKs are transmembrane proteins that have a domain outside of the cell that binds to the growth factor and a domain within the cell that has tyrosine kinase activity, hence the name “receptor tyrosine kinase (RTK).” This enzymatic activity adds a phosphate to a tyrosine residue of target proteins and starts a typical signal transduction pathway (referred to in the paper as “canonical”) leading to the usual biological responses (proliferation, survival, migration, etc.)
MedicalResearch.com: What are the main findings?
Response: There are two main findings:
- First, the paper focuses very much on what these signaling pathways do during craniofacial development, and loss of the two receptors leads to major defects in closure of the face, and mandibular hypoplasia. These defects are more severe but relevant to birth defects such as cleft lip/palate or micrognathia (small lower jaw).
- The authors show that mice carrying mutations that prevent the receptors from engaging the canonical signal transduction pathway have much less severe defects that mice that do not express the receptors at all, demonstrating that these receptors have additional functions. The authors identify one such function as cell adhesion. As a result of the defect in cell adhesion, they further show that cells with no receptors cannot stick to a network of secreted proteins (then extracellular matrix) or to each other. These functions are retained in cells derived from mutants which cannot initiate the typical signal transduction pathway.
MedicalResearch.com: What should readers take away from your report?
Response: Two take home messages:
- FGFs are important in craniofacial development (relevance to birth defects).
- The FGF receptors have additional function beyond the typical ones in signal transduction that we did not know about. This is important to know for therapeutic treatments that aim to suppress their activity.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: The laboratory will continue to explore the cell adhesion mechanisms.
FGF signaling regulates development by processes beyond canonical pathways
Published in Advance November 12, 2020, doi:
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