Establishment of hindbrain segmental identity requires signaling by FGF3 and FGF8.
The hindbrain (brainstem) of all vertebrates follows a segmental developmental strategy and has been the focus of intense study not only for its intrinsic interest but also as a model for how more complex regions of the brain are patterned. Segmentation ultimately serves to organize the development of neuronal populations and their projections, and regional diversity is achieved through each segment having its own identity. The latter being established through differential expression of a hierarchy of transcription factors, including Hox genes, Krox20, and Kreisler/Valentino. Here we identify a novel signaling center in the zebrafish embryo that arises prior to establishment of segmental patterning and which is located centrally within the hindbrain territory in a region that corresponds to the presumptive rhombomere 4. We show that signaling from this region by two members of the FGF family of secreted proteins, FGF3 and FGF8, is required to establish correct segmental identity throughout the hindbrain and for subsequent neuronal development. Spatiotemporal studies of Fgf expression suggest that this patterning mechanism is conserved during hindbrain development in other vertebrate classes.
Walshe
Jennifer
J
MRC Centre for Developmental Neurobiology, New Hunt's House, King's College London, Guy's Campus, United Kingdom.
Maroon
Habib
H
McGonnell
Imelda M
IM
Dickson
Clive
C
Mason
Ivor
I
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D051767:Early Growth Response Protein 2; D036388:Ephrin-B2 / Q000096:biosynthesis; D051518:Fibroblast Growth Factor 3; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012249:Rhombencephalon / Q000196:embryology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins; D000099266:Engrailed 2 Protein
D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; D036388:Ephrin-B2; D051518:Fibroblast Growth Factor 3; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C513242:Etv5 protein, mouse; C489197:Fgf3 protein, mouse; C079428:en2a protein, zebrafish; D000099266:Engrailed 2 Protein; C513244:etv5b protein, zebrafish; C489200:fgf3 protein, zebrafish; C489831:hoxa2b protein, zebrafish