Brain-specific angiogenesis inhibitor 1 is expressed in the Myo/Nog cell lineage

PLoS One. 2020 Jul 2;15(7):e0234792. doi: 10.1371/journal.pone.0234792. eCollection 2020.


The Myo/Nog cell lineage was discovered in the chick embryo and is also present in adult mammalian tissues. The cells are named for their expression of mRNA for the skeletal muscle specific transcription factor MyoD and bone morphogenetic protein inhibitor Noggin. A third marker for Myo/Nog cells is the cell surface molecule recognized by the G8 monoclonal antibody (mAb). G8 has been used to detect, track, isolate and kill Myo/Nog cells. In this study, we screened a membrane proteome array for the target of the G8 mAb. The array consisted of >5,000 molecules, each synthesized in their native confirmation with appropriate post-translational modifications in a single clone of HEK-293T cells. G8 mAb binding to the clone expressing brain-specific angiogenesis inhibitor 1 (BAI1) was detected by flow cytometry, re-verified by sequencing and validated by transfection with the plasmid construct for BAI1. Further validation of the G8 target was provided by enzyme-linked immunosorbent assay. The G8 epitope was identified by screening a high-throughput, site directed mutagenesis library designed to cover 95-100% of the 954 amino acids of the extracellular domain of the BAI1 protein. The G8 mAb binds within the third thrombospondin repeat of the extracellular domain of human BAI1. Immunofluorescence localization experiments revealed that G8 and a commercially available BAI1 mAb co-localize to the subpopulation of Myo/Nog cells in the skin, eyes and brain. Expression of the multi-functional BAI1 protein in Myo/Nog cells introduces new possibilities for the roles of Myo/Nog cells in normal and diseased tissues.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Angiogenic Proteins / biosynthesis*
  • Angiogenic Proteins / chemistry
  • Angiogenic Proteins / genetics
  • Angiogenic Proteins / immunology
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibody Specificity
  • Antigen-Antibody Reactions
  • Brain / cytology
  • Carrier Proteins / analysis
  • Cell Lineage
  • Epitopes / immunology
  • Eye Proteins / biosynthesis
  • Eye Proteins / chemistry
  • Eye Proteins / genetics
  • Eye Proteins / immunology
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Molecular
  • Muscle Development
  • MyoD Protein / analysis
  • Myofibroblasts / metabolism*
  • Organ Specificity
  • Protein Conformation
  • Protein Domains
  • Rabbits
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / biosynthesis*
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / immunology
  • Repetitive Sequences, Amino Acid
  • Skin / cytology
  • Species Specificity
  • Tattooing
  • Young Adult


  • ADGRB1 protein, human
  • Angiogenic Proteins
  • Antibodies, Monoclonal
  • Carrier Proteins
  • Epitopes
  • Eye Proteins
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Receptors, G-Protein-Coupled
  • noggin protein

Grant support

This work was supported by an anonymous donation for the Myo/Nog cell program project to MG-W and AB-N. The donor was not a tobacco company. The donor provided partial support of salaries for MG-W, AB-N and JG. Support also was provided for supplies and reagents. The authors are not aware of any competing interests. The identity of the donor is not relevant to editors or reviewers’ assessment of the validity of the work. Funding also was provided by Genisphere, LLC, Employees of Genisphere, including JB, LC, LG and RG, participated in study design, data collection and analysis, the decision to publish and preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. The funder provided support in the form of salaries for authors.