Nab proteins mediate a negative feedback loop controlling Krox-20 activity in the developing hindbrain.
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.
Mechta-Grigoriou
F
F
Unité 368 de l'Institut National de la Santé et de la Recherche Médicale, Ecole Normale Supérieure, Paris France.
Garel
S
S
Charnay
P
P
D016475:3T3 Cells; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D051767:Early Growth Response Protein 2; D005246:Feedback; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009363:Neoplasm Proteins; D012097:Repressor Proteins / Q000235:genetics*; D012249:Rhombencephalon / Q000196:embryology* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D015027:Zebrafish
D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; C491000:NAB2 protein, human; C490624:Nab1 protein, mouse; C099945:Nab2 protein, mouse; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D014157:Transcription Factors