Somatic motoneurone specification in the hindbrain: the influence of somite-derived signals, retinoic acid and Hoxa3.
We have investigated the mechanisms involved in generating hindbrain motoneurone subtypes, focusing on somatic motoneurones, which are confined to the caudal hindbrain within rhombomeres 5-8. Following heterotopic transplantation of rhombomeres along the rostrocaudal axis at various developmental stages, we have found that the capacity of rhombomeres to generate somatic motoneurones is labile at the neural plate stage but becomes fixed just after neural tube closure, at stage 10-11. Grafting of somites or retinoic acid-loaded beads beneath the rostral hindbrain induced the formation of somatic motoneurones in rhombomere 4 only, and Hox genes normally expressed more caudally (Hoxa3, Hoxd4) were induced in this region. Targeted overexpression of Hoxa3 in the rostral hindbrain led to the generation of ectopic somatic motoneurones in ventral rhombomeres 1-4, and was accompanied by the repression of the dorsoventral patterning gene Irx3. Taken together, these observations suggest that the somites, retinoic acid and Hox genes play a role in patterning somatic motoneurones in vivo.
Guidato
Sonia
S
MRC Centre for Developmental Neurobiology, 4th Floor New Hunt's House, King's College, Guy's Campus, London SE1 1UL, UK.
Prin
Fabrice
F
Guthrie
Sarah
S
D000818:Animals; D016380:Brain Tissue Transplantation; D019070:Cell Lineage; D002642:Chick Embryo; D002678:Chimera; D018274:Electroporation; D004627:Embryonic Induction; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D060850:LIM-Homeodomain Proteins; D008648:Mesoderm / Q000502:physiology; D008863:Microspheres; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011784:Quail / Q000196:embryology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012249:Rhombencephalon / Q000166:cytology* / Q000196:embryology* / Q000254:growth & development / Q000637:transplantation; D019170:Somites / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*; D029961:Zebrafish Proteins
C489832:HOXA3 protein, human; D018398:Homeodomain Proteins; C516210:ISL2 protein, human; C091135:Isl-2 protein, vertebrate; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C489831:hoxa2b protein, zebrafish; C490404:isl2a protein, zebrafish; D014212:Tretinoin