A postmitotic role for Isl-class LIM homeodomain proteins in the assignment of visceral spinal motor neuron identity.
LIM homeobox genes have a prominent role in the regulation of neuronal subtype identity and distinguish motor neuron subclasses in the embryonic spinal cord. We have investigated the role of Isl-class LIM homeodomain proteins in motor neuron diversification using mouse genetic methods. All spinal motor neuron subtypes initially express both Isl1 and Isl2, but Isl2 is rapidly downregulated by visceral motor neurons. Mouse embryos lacking Isl2 function exhibit defects in the migration and axonal projections of thoracic level motor neurons that appear to reflect a cell-autonomous switch from visceral to somatic motor neuron character. Additional genetic mutations that reduce or eliminate both Isl1 and Isl2 activity result in more pronounced defects in visceral motor neuron generation and erode somatic motor neuron character. Thus, an early phase of high Isl expression and activity in newly generated motor neurons permits the diversification of visceral and somatic motor neuron subtypes in the developing spinal cord.
Thaler
Joshua P
JP
Gene Expression Laboratory, The Salk Institute, La Jolla, CA 92037, USA.
Koo
Sonya J
SJ
Kania
Artur
A
Lettieri
Karen
K
Andrews
Shane
S
Cox
Christopher
C
Jessell
Thomas M
TM
Pfaff
Samuel L
SL
D000110:Acetylcholinesterase / Q000378:metabolism; D000375:Aging; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000201:enzymology; D015139:Blotting, Southern; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D004622:Embryo, Mammalian; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins; D007763:Lac Operon; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D009046:Motor Neurons / Q000145:classification / Q000502:physiology*; D009154:Mutation; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D010525:Peripheral Nerves / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology / Q000637:transplantation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014781:Viscera / Q000196:embryology
D000596:Amino Acids; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C094898:Lhx3 protein; D014157:Transcription Factors; C088975:Vsx2 protein, mouse; C098463:dolaisoleucine; C084059:Hb9 protein, mouse; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D000110:Acetylcholinesterase