A functional interaction between Irx and Meis patterns the anterior hindbrain and activates krox20 expression in rhombomere 3.
Patterning of the vertebrate hindbrain involves a segmentation process leading to the formation of seven rhombomeres along the antero-posterior axis. While recent studies have shed light on the mechanisms underlying progressive subdivision of the posterior hindbrain into individual rhombomeres, the early events involved in anterior hindbrain patterning are still largely unknown. In this paper we demonstrate that two zebrafish Iroquois transcription factors, Irx7 and Irx1b, are required for the proper formation and specification of rhombomeres 1 to 4 and, in particular, for krox20 activation in r3. We also show that Irx7 functionally interacts with Meis factors to activate the expression of anterior hindbrain markers, such as hoxb1a, hoxa2 and krox20, ectopically in the anterior neural plate. Then, focusing on krox20 expression, we show that the effect of Irx7 and Meis1.1 is mediated by element C, a conserved cis-regulatory element involved in krox20 activation in the hindbrain. Together, our data point to an essential function of Iroquois transcription factors in krox20 activation and, more generally, in anterior hindbrain specification.
Stedman
Aline
A
CNRS UMR7622, Laboratoire de Biologie du Développement, Université Pierre et Marie Curie, Bâtiment C 7ème étage, Boîte 24, 9 quai Saint Bernard, 75005 Paris, France.
Lecaudey
Virginie
V
Havis
Emmanuelle
E
Anselme
Isabelle
I
Wassef
Michel
M
Gilardi-Hebenstreit
Pascale
P
Schneider-Maunoury
Sylvie
S
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019521:Body Patterning / Q000502:physiology*; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D054258:Neural Plate / Q000033:anatomy & histology / Q000502:physiology; D050436:Regulatory Elements, Transcriptional; D012249:Rhombencephalon / Q000033:anatomy & histology / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D051767:Early Growth Response Protein 2; C101121:HOXB1 homeodomain protein; D018398:Homeodomain Proteins; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D014157:Transcription Factors; D029961:Zebrafish Proteins; C489831:hoxa2b protein, zebrafish; C459599:irx1b protein, zebrafish; C459598:irx7 protein, zebrafish; C508763:meis1b protein, zebrafish