The Meis3 protein and retinoid signaling interact to pattern the Xenopus hindbrain.
In Xenopus embryos, proper hindbrain formation requires activities of both XMeis3 protein and retinoic acid (RA) signaling. In this study, we show that XMeis3 protein and RA signaling differentially interact to regulate hindbrain patterning. The knockdown of XMeis3 protein prevented RA-caudalizing activity from inducing hindbrain marker expression in both explants and embryos. In contrast, inhibition of RA signaling differentially modulated XMeis3 activity. Target genes that are jointly activated by either RA or XMeis3 activities could not be efficiently induced by XMeis3 when RA signaling was inhibited. However, transcription of an XMeis3 target gene that is not an RA target gene was hyper-induced in the absence of retinoid signaling. Target genes jointly induced by RA or XMeis3 protein were synergistically activated in the presence of both activities, while RA treatment inhibits the ability of XMeis3 to activate transcription of neural genes that are not RA targets. HoxD1, an RA direct-target gene was also identified as an XMeis3 direct-target gene. HoxD1 protein acts downstream of XMeis3 to induce hindbrain marker gene transcription. To pattern the hindbrain, RA requires functional XMeis3 protein activity. XMeis3 protein appears crucial for initial hindbrain induction, whereas RA signaling defines the spatial limits of hindbrain gene expression by modifying XMeis3 protein activity.
Dibner
Charna
C
Department of Biochemistry, Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Haifa 31096, Israel.
Elias
Sarah
S
Ofir
Rachel
R
Souopgui
Jacob
J
Kolm
Peggy J
PJ
Sive
Hazel
H
Pieler
Tomas
T
Frank
Dale
D
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000378:metabolism* / Q000502:physiology; D017403:In Situ Hybridization; D008156:Luciferases; D008845:Microinjections; D010957:Plasmids; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012249:Rhombencephalon / Q000196:embryology*; D015398:Signal Transduction / Q000502:physiology*; D014212:Tretinoin / Q000378:metabolism* / Q000502:physiology; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology*
D018398:Homeodomain Proteins; C491174:Meis3 protein, Xenopus; D029867:Xenopus Proteins; D014212:Tretinoin; D008156:Luciferases