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Publication : Ptf1a directly controls expression of immunoglobulin superfamily molecules Nephrin and Neph3 in the developing central nervous system.

First Author  Nishida K Year  2010
Journal  J Biol Chem Volume  285
Issue  1 Pages  373-80
PubMed ID  19887377 Mgi Jnum  J:158304
Mgi Id  MGI:4438526 Doi  10.1074/jbc.M109.060657
Citation  Nishida K, et al. (2010) Ptf1a directly controls expression of immunoglobulin superfamily molecules Nephrin and Neph3 in the developing central nervous system. J Biol Chem 285(1):373-80
abstractText  Ptf1a, a basic helix-loop-helix transcription factor, plays an indispensable role for cell fate specification of subsets of neurons in the developing central nervous system. However, downstream molecules induced by Ptf1a during neural development have not been well characterized. In the present study, we identified immunoglobulin superfamily molecules, Nephrin and Neph3, as direct downstream targets of Ptf1a. First, the expression domains of Nephrin and Neph3 closely resembled those of Ptf1a in the developing retina, hypothalamus, cerebellum, hindbrain, and spinal cord. Second, Ptf1a bound directly to a PTF-binding motif in the 5'-flanking region of Nephrin and Neph3 genes. Third, Ptf1a activated transcription driven by the 5'-flanking region of these genes. Finally, the expression of Nephrin and Neph3 was lost in Ptf1a-null mice, whereas ectopic expression of Nephrin and Neph3 was induced by forced expression of Ptf1a. We provided further evidence that Nephrin and Neph3 could interact homophilically and heterophilically, suggesting that Nephrin and Neph3 might regulate certain developmental aspects of Ptf1a-positive neurons as homo- or heterooligomers.
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