An Fgf8-dependent bistable cell migratory event establishes CNS asymmetry.
Neuroanatomical and functional asymmetries are universal features of the vertebrate CNS, but how asymmetry is generated is unknown. Here we show that zebrafish fgf8 mutants do not elaborate forebrain asymmetries, demonstrated by the failure of the parapineal nucleus to migrate from its initial midline position to the left side of the brain. Local provision of Fgf8 restores the asymmetric migration of parapineal cells, usually to the left, irrespective of the location of the Fgf8 source. This laterality bias is due to left-sided Nodal signaling and when the bias in Nodal signaling is removed, parapineal cells migrate toward the source of Fgf8 protein. This study presents a mechanism for breaking neuroanatomical symmetry through Fgf8-dependent regulation of bistable left- or right-sided migration of the parapineal. The combined action of Fgf and Nodal signals ensures the establishment of neuroanatomical asymmetries with consistent laterality.
Regan
Jennifer C
JC
Department of Cell and Developmental Biology, UCL, Gower Street, London WC1E6BT, UK.
Concha
Miguel L
ML
Roussigne
Myriam
M
Russell
Claire
C
Wilson
Stephen W
SW
D000818:Animals; D019521:Body Patterning / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002490:Central Nervous System / Q000033:anatomy & histology* / Q000196:embryology* / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015027:Zebrafish / Q000033:anatomy & histology* / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D051858:Forkhead Transcription Factors; D055457:Nodal Protein; D016376:Oligonucleotides, Antisense; D011993:Recombinant Fusion Proteins; D029961:Zebrafish Proteins; C517774:fgf8a protein, zebrafish; C491002:foxd3 protein, zebrafish; D005346:Fibroblast Growth Factors