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Publication : Nab proteins mediate a negative feedback loop controlling Krox-20 activity in the developing hindbrain.

First Author  Mechta-Grigoriou F Year  2000
Journal  Development Volume  127
Issue  1 Pages  119-28
PubMed ID  10654606 Mgi Jnum  J:55208
Mgi Id  MGI:1349348 Doi  10.1242/dev.127.1.119
Citation  Mechta-Grigoriou F, et al. (2000) Nab proteins mediate a negative feedback loop controlling Krox-20 activity in the developing hindbrain. Development 127(1):119-28
abstractText  The developing vertebrate hindbrain is transiently subdivided along the anterior-posterior axis into metameric units, called rhombomeres (r). These segments constitute units of lineage restriction and display specific gene expression patterns. The transcription factor gene Krox-20 is restricted to r3 and r5, and is required for the development of these rhombomeres. We present evidence that Krox-20 transcriptional activity is under the control of a negative feedback mechanism in the hindbrain. This regulatory loop involves two closely related proteins, Nabl and Nab2, previously identified as antagonists of Krox-20 transcriptional activity in cultured cells. Here we show that in the mouse hindbrain, Nab1 and Nab2 recapitulate the Krox-20 expression pattern and that their expression is dependent on Krox-20 function. Furthermore, misexpression of Nab1 or Nab2 in zebrafish embryos leads to alterations in the expression patterns of several hindbrain markers, consistent with an inhibition of Krox-20 activity. Taken together, these data indicate that Krox-20 positively regulates the expression of its own antagonists and raise the possibility that this negative feedback regulatory loop may play a role in the control of hindbrain development.
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