PDGFRβ regulates craniofacial development through homodimers and functional heterodimers with PDGFRα

Katherine A Fantauzzo1, Philippe Soriano1

  • 1Department of Cell Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.

Genes & Development
|November 19, 2016
PubMed

Insights

Platelet-derived growth factor receptor beta (PDGFRβ) plays a crucial role in craniofacial development. Its interaction with PDGFRα influences facial structure, and disruptions lead to birth defects.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Craniofacial development is vital, with disruptions causing common birth defects.
  • Platelet-derived growth factor receptor alpha (PDGFRα) is known to be involved.
  • The function of PDGFRβ in murine craniofacial development is not well understood.

Purpose of the Study:

  • To investigate the role of PDGFRβ in murine craniofacial development.
  • To explore the interaction between PDGFRα and PDGFRβ in neural crest cells.
  • To elucidate the signaling mechanisms of PDGF receptors in craniofacial morphogenesis.

Main Methods:

  • Analyzing Pdgfrb knockout mouse models in neural crest lineage.
  • Examining craniofacial phenotypes including nasal septum width and palatal shelf development.
  • Investigating genetic interactions and physical associations between PDGFRα and PDGFRβ.

Main Results:

  • PDGFRα and PDGFRβ are coexpressed in craniofacial mesenchyme.
  • PDGFRβ ablation in neural crest cells causes nasal septum defects and delayed palatal development.
  • Double mutants exhibit more severe facial clefting, indicating genetic interaction.
  • PDGFRα and PDGFRβ form functional heterodimers with unique signaling properties.

Conclusions:

  • PDGFRβ is essential for normal craniofacial development.
  • PDGFRα and PDGFRβ form functional heterodimers, revealing a novel PDGF signaling pathway.
  • This study uncovers a new mode of PDGF family signaling in vertebrate development.

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.8K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
5.6K
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
12.1K
Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
6.4K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.9K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
10.3K