Platelet derived growth factor B gene expression in the Xenopus laevis developing central nervous system

Abstract

Platelet-derived growth factor B (PDGF-B) belongs to the mitogen and growth factor family and like the other members it has many roles in cell differentiation, proliferation and migration during development, adult life and in pathological conditions. Among them it has been observed that aberrant PDGF signalling is frequently linked to glioma development and progression, and Pdgf-b over-expression in mouse neural progenitors leads to the formation of gliomas. Despite this evidence, the mechanisms underlying PDGF-B driven tumorigenesis and its role during brain development are not fully understood. In order to contribute to clarifying possible new roles of pdgf-b signalling, we present here the embryonic gene expression pattern of pdgf-b, so far unknown in early vertebrate development. By using Xenopus laevis as a model system we performed qRT-PCR and whole mount in situ hybridization. Pdgf-b mRNA is expressed in discrete regions of the developing central nervous system, in the cranial nerve placodes and in the notochord. We also compared the gene expression of pdgf-b with that of its receptor pdgfr-a suggesting so far unsuspected roles for this signalling pathway during the development of specific embryonic structures. KEY WORDS: PDGF-B, PDGF receptor a, central nervous system, neural crest, Xenopus laevisPlatelet-derived growth factor (PDGF) family comprises two tyrosine kinase receptors (PDGFR-a and -b) and four ligands (PDGF-A, -B, -C, and -D) that form homodimers or the heterodimer AB (Demoulin and Essaghir, 2014). The active ligand-receptor complex consists of two receptor chains associated with one dimeric ligand. While PDGFR-a binds to all PDGF isoforms except for PDGF-DD, PDGFR-b binds only to PDGF-BB and -DD (Fig.1). Also a heterodimeric ab receptor has been reported that binds to PDGF-AB, -BB and possibly -CC and -DD (Demoulin and Essaghir, 2014). The members of this family have been extensively studied for more than 30 years in development, adult homeostasis and disease (Heldin, 2013, Heldin, 2014, Hoch and Soriano, 2003. Pdgf-a expression was recently characterized in mouse tissues and in early embryonic development, showing its involvement in developmental processes including gastrulation and craniofacial development (Andrae et al., 2014, Eberhart et al., 2008. On the contrary, for pdgf-b the only information available mainly concern its role during embryonic angiogenesis (Hoch and Soriano, 2003, Leveen et al., 1994), and a complete gene expression pattern in vertebrate embryogenesis is still lacking. Functional studies using a knock out mouse for pdgf-b showed abnormal kidney glomeruli, heart and blood vessel dilation, anemia, thrombocytopenia, haemorrhages and perinatal death (Betsholtz, 1995, Leveen et al., 1994. However, in this mutant line, BB homodimer and AB heterodimer were simultaneously abrogated, making difficult to precisely define the specific role of pdgf-b alone during embryogenesis. Furthermore, due to extensive perinatal haemorrhages, other possible phenotypes caused by the...

Pdgfra and Pdgfrb Genetically Interact in the Murine Neural Crest Cell Lineage to Regulate Migration and Proliferation

“…Following initiation of the epithelial-to-mesenchymal transition, migrating NCCs chemotax toward PDGF-A ligand in the surrounding tissue, resulting in directional migration (Bahm et al, 2017). The ligand pdgfb is also expressed in tissues adjacent to migrating NCCs in Xenopus embryos (Giannetti et al, 2016) and knock-down of this ligand results in impaired cNCC migration and defective development of the craniofacial cartilages and cranial nerves in a subset of morpholino-injected embryos (Corsinovi et al, 2019). In zebrafish, pdgfra is similarly expressed by pre-migratory and migratory cNCCs, while its ligand pdgfaa is correspondingly expressed at early stages in the midbrain and later in the oral ectoderm (Eberhart et al, 2008).…”

PDGF‐B: The missing piece in the mosaic of PDGF family role in craniofacial development

“…A new hint emerged from our recent analysis of the pdgf-b gene-expression profile in Xenopus embryos. 21 We showed that pdgf-b mRNA was not expressed in NCCs but in adjacent territories, indicating that pdgf-b could contribute to the early phases of NCC migration, given that these cells express, at least, pdgfr-α. In Xenopus, cranial NCCs migrate from the mesencephalic and rhombencephalic regions of the central nervous system (CNS) toward the branchial pouches, starting at late neurula stage (stage 19).…”

“…For all these reasons, the role of pdgf‐b during embryonic life remains elusive and, so far, not fully understood. A new hint emerged from our recent analysis of the pdgf‐b gene‐expression profile in Xenopus embryos . We showed that pdgf‐b mRNA was not expressed in NCCs but in adjacent territories, indicating that pdgf‐b could contribute to the early phases of NCC migration, given that these cells express, at least, pdgfr‐α.…”

“…Pdgf‐b expression domain remained in close proximity to NCCs that are still migrating at this stage but never overlaps them. The presence of pdgf‐b in the facial placode suggested that it might contribute to the correct formation of the facial nerve that is composed of an ectodermal derivative, the placode, and NCCs …”

“…The presence of pdgf-b in the facial placode suggested that it might contribute to the correct formation of the facial nerve that is composed of an ectodermal derivative, the placode, and NCCs. 21 As pdgf-b is expressed in specific embryonic territories adjacent to pdgfr-α-expressing NCCs, we hypothesize that this ligand could also participate in the orchestration of NCC development. To test our hypothesis, we aimed to perform gene loss-of-function experiments in Xenopus embryos.…”