Integration of telencephalic Wnt and hedgehog signaling center activities by Foxg1.
The forebrain is patterned along the dorsoventral (DV) axis by Sonic Hedgehog (Shh). However, previous studies have suggested the presence of an Shh-independent mechanism. Our study identifies Wnt/beta-catenin-activated from the telencephalic roof-as an Shh-independent pathway that is essential for telencephalic pallial (dorsal) specification during neurulation. We demonstrate that the transcription factor Foxg1 coordinates the activity of two signaling centers: Foxg1 is a key downstream effector of the Shh pathway during induction of subpallial (ventral) identity, and it inhibits Wnt/beta-catenin signaling through direct transcriptional repression of Wnt ligands. This inhibition restricts the dorsal Wnt signaling center to the roof plate and consequently limits pallial identities. Concomitantly to these roles, Foxg1 controls the formation of the compartment boundary between telencephalon and basal diencephalon. Altogether, these findings identify a key direct target of Foxg1, and uncover a simple molecular mechanism by which Foxg1 integrates two opposing signaling centers.
Danesin
Catherine
C
Medical Research Council Centre for Developmental Neurobiology, King's College London, London, UK.
Peres
João N
JN
Johansson
Marie
M
Snowden
Victoria
V
Cording
Amy
A
Papalopulu
Nancy
N
Houart
Corinne
C
D000818:Animals; D019521:Body Patterning / Q000187:drug effects; D005399:Fishes; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053823:Hedgehog Proteins / Q000378:metabolism*; D008024:Ligands; D008322:Mammals; D054259:Neural Tube / Q000187:drug effects / Q000196:embryology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013687:Telencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D051858:Forkhead Transcription Factors; D053823:Hedgehog Proteins; D008024:Ligands; D016376:Oligonucleotides, Antisense; D012097:Repressor Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C540570:foxg1a protein, zebrafish