Functional analysis of homeobox genes in neuromere development : Mouse molecular genetical approch

• Project/Area Number: 09680750
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Kitasato University
• Principal Investigator: HANAOKA Kazunori Kitasato University, School of Science, Professor, 理学部, 教授 (40189577)
• Co-Investigator(Kenkyū-buntansha): KITAMURA Kunio Mitsubishi Kagaku, Institute of Life Science, Cheif Researcher, 生命科学研究所, 主任研究員 ; UCHIYAMA Koji Kitasato University, School of Science, Assistant, 理学部, 助手 (20276174)
• Project Period (FY): 1997 – 1998
• Project Status: Completed (Fiscal Year 1998)
• Budget Amount: ¥2,900,000 (Direct Cost: ¥2,900,000); Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: homeobox gene / neural crest / somite / hindbrain / muscle differentiation / gene targetting / transgenic mouse / mouse molecular genetics / 筋分化 / 脳神経 / ホメオボックス / 発生工学

Research Abstract

(1) Somites are the source of hypaxial musculature including skeletal muscles of the limb, tongue and the trunk. To get insight into the function of mouse Lbxl homeobox gene in the early somitic mesoderni differentiation, in situhybridization analyses was performed. At 4-6 somite stage (8dpc), Lbxl was first expressed in the lateral portion of the epithelial somite and of dermomyotomal epithelium. This was contrast to the expression of myf-5 in the medial region of the somite. Then the lateral expression of Lbxl in somitic mesoderm occurred regionally along the anterior-posterior body axis. Later at 10 dpc (stage 1 for limb bud development) Lbxl-positive migrating cells originated from the lateral dermomyotomal lips at occipital, forelimb and hindlinib levels. They also expressed Pax-3 and c-met known as markers of the migrating limb muscle precursor cells. In stage 4 hindlimb bud (11.5 dpc), the dorsal and ventral muscle precursor populations expressed Lbxl. In stage 8 forelimb buds ( 12.5 dpc), Lbxl expression was reduced in the proximal muscle masses where the highly expression of myogenin accompanying the muscle differentiation was detected. These results suggest that mouse Lbxl might be involved in the commitment or determination of a muscle cell subpopulation during the hypaxial musculature development.
(2) cHox11L2, the chick counterpart of mouse Hox11L2, was isolated. cHox11L2 was expressed in the developing chick peripheral nervous system, i. e. sensory cranial nerves of the placodal ectoderm origin, sympathetic ganglia, dorsal root ganglia and enteric ganglia as well as the limited population of the spinal cord. In neuronal derivatives of the neural crest, dHox11L2 was expressed in the postmigratory cells and not in the migrating neural crest cells. Furthermore, Intense signals of cHox11L2 mRNA were detected even in the spinal cord and the dorsal root of 10 day embryo. These results suggest that cHox11L2 might play a role in the determination and/or maintenance of neuronal differentiation during chick nervous system development.

Research Products

• [Publications] Kameya, S, Miyagoe Y, Nonaka I, Ikemoto T, Endo M, Hanaoka K, Nabeshima Y and Takeda S.: "alphal-syntrophin gene disruptionresults in the absence of neuronal-type nitric oxide synthetase at the salcolemma, but does not induce muscle" J Biol Chem. 274, No4. 2192-2200 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Uchiyama K. Ishikawa A. and Hanaoka K.: "Expression of Lbxl involved in the hypaxial musculature formation of the mouse embryo" J Exp Zool. In press.
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] K.Uchiyama, R.Ohtuka and Hanaoka K.: "cHox11L2, a Hox11 related gene, is expressed in the peripheral nervous system and subpopulation of spinal cord during chick development" Neurosci. Lett. In press.
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kameya S., Miyagoe Y., Nonaka I., Ikemoto T., Endo M., Hanaoka K., Nabeshima Y., and Takeda S.: "alphal-syntrophin gene disruptionresults in the absence of neuronal-type nitric oxide synthetase at the salcolemma, but does not induce muscle degeneration" J Biol Chem. 274, No4. 2192-2200 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Uchiyama, K., Ishikawa, A.and Hanaoka, K.: "Expression of Lbx1 involved in the hypaxial musculature formation of the mouse embryo" J Exp Zool. (in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] K.Uchiyama. R.Ohtuka and Hanaoka, K.: "cHox11L2, a Hox11 related gene, is expressed in the peripheral nervous system and subpopulation of spinal cord during chick development" Neurosci.Lett. (in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] K.Tomizuka et al.: "Functional expression and germlinetransmission of human chromosome fragment in chimeric mice" Nature Genet. 16. 133-143 (1977)
• [Publications] Miyagoe Y et al.: "Laminin α 2 chain null mutant mice bytargeted disrupnon of the Lama 2 gene:A new model of merosin-deficient congenital muscular dystrophy" FEBS Letters. 415. 33-39 (1977)
• [Publications] Uchiyama K,Hayasaka M & Hanaoka K: "CHOXIIL2,a HoxII related gene,is expressed in the chick developing peripheral nervous system of the neural crest origin" (発表予定).