In order to identify new molecules that might play a role in regionalspecification of the nervous system, we generated and characterizedmonoclonal antibodies (mAbs) that have positionally-restricted labelingpatterns.
The FORSE-1 mAb was generated using a strategy designed to producemAbs against neuronal cell surface antigens that might be regulated byregionally-restricted transcription factors in the developing central nervoussystem (CNS). FORSE-1 staining is enriched in the forebrain as compared tothe rest of the CNS until E18. Between E11.5-E13.5, only certain areas of theforebrain are labeled. There is also a dorsoventrally-restricted region oflabeling in the hindbrain and spinal cord. The mAb labels a largeproteoglycan-like cell-surface antigen (>200 kD). The labeling pattern ofFORSE-1 is conserved in various mammals and in chick.
To determine whether the FORSE-1 labeling pattern is similar to thatof known transcription factors, the expression of BF-1 and Dlx-2 wascompared with FORSE-1. There is a striking overlap between BF-1 andFORSE-1 in the telencephalon. In contrast, FORSE-1 and Dlx-2 have verydifferent patterns of expression in the forebrain, suggesting that regulation byDlx-2 alone cannot explain the distribution of FORSE-1. They do, however,share some sharp boundaries in the diencephalon. In addition, FORSE-1identifies some previously unknown boundaries in the developing forebrain.Thus, FORSE-1 is a new cell surface marker that can be used to subdivide theembryonic forebrain into regions smaller than previously described,providing further complexity necessary for developmental patterning.
I also studied the expression of the cell surface protein CD9 in thedeveloping and adult rat nervous system. CD9 is implicated in intercellularsignaling and cell adhesion in the hematopoetic system. In the nervoussystem, CD9 may perform similar functions in early sympathetic ganglia,chromaffin cells, and motor neurons, all of which express the protein. Thepresence of CD9 on the surfaces of Schwann cells and axons at the appropriatetime may allow the protein to participate in the cellular interactions involvedin myelination.
