A central role for Islet1 in sensory neuron development linking sensory and spinal gene regulatory programs.
We used conditional knockout strategies in mice to determine the developmental events and gene expression program regulated by the LIM-homeodomain factor Islet1 in developing sensory neurons. Early development of the trigeminal and dorsal root ganglia was grossly normal in the absence of Islet1. From E12.5 onward, however, Isl1 mutant embryos showed a loss of the nociceptive markers TrkA and Runx1 and a near absence of cutaneous innervation. Proprioceptive neurons characterized by the expression of TrkC, Runx3 and Etv1 were relatively spared. Microarray analysis of Isl1 mutant ganglia revealed prolonged expression of developmental regulators that are normally restricted to early sensory neurogenesis and ectopic expression of transcription factors that are normally found in the CNS, but not in sensory ganglia. Later excision of Isl1 did not reactivate early genes, but resulted in decreased expression of transcripts related to specific sensory functions. Together these results establish a central role for Islet1 in the transition from sensory neurogenesis to subtype specification.
Department of Medicine, University of California San Diego, La Jolla, California 93093, USA.
Yunfu
Y
Sun
Iain M
IM
Dykes
Xingqun
X
Liang
S Raisa
SR
Eng
Sylvia M
SM
Evans
Eric E
EE
Turner
D000818:Animals; D019521:Body Patterning / Q000502:physiology; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D002490:Central Nervous System / Q000378:metabolism; D050657:Core Binding Factor alpha Subunits / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D004965:Estrogen Antagonists / Q000009:adverse effects; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis / Q000379:methods; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D012249:Rhombencephalon / Q000196:embryology / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D013629:Tamoxifen / Q000009:adverse effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000166:cytology / Q000196:embryology
D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins; D004965:Estrogen Antagonists; C490641:Etv1 protein, mouse; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D013629:Tamoxifen; D020917:Receptor, trkA; D001973:Bromodeoxyuridine