1998 Fiscal Year Final Research Report Summary
Embryological and teratological analyzes of genes acting in limb morphogenesis
| Project/Area Number |
08457006
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General anatomy (including Histology/Embryology)
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
YASUDA Mineo Hiroshima Univ.Fac.Med., Dept.Anat., Prof., 医学部, 教授 (50079688)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUI Kohji Hiroshima Univ.Fac.Med., Dept.Anat., Assistant, 医学部, 助手 (80183945)
YAMASHITA Keisuke Hiroshima Univ.Fac.Med., Dept.Anat., Assoc.Prof., 医学部, 助教授 (40166666)
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| Project Period (FY) |
1996 – 1998
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| Keywords | limb morphogenesis / pad / meromelia mouse / En-1 gene / Wnt-7a gene / dorso-ventral axis / apical ectodermal ridge / retinoic acid |
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| Research Abstract |
The ventral surface of mouse limbs is characterized by pads. Abnormal pad patters may be induced by mutant genes or environmental agents. Observation of pads in mutant mice "meromelia" revealed dorsalization of the ventral surface of limbs. Developing limb buds of meromelia were examined by whole mount in situ hybridization with probes for En-1 (a ventral marker) and Wnt-7a (a dorsal marker). In meromelia limbs, the En-1 expressing area was reduced, whereas the Wnt-7a expressing area was enlarged to the ventral surface. The area expressing Fgf-8 and Fgf-4, which are markers for the apical ectodermal ridge (AER), were located in the normal position, i.e., the apex of limb buds. These findings cast doubts on the notion that the AER is formed at the interface of En-1 and Wnt- 7a, and suggest that En-1 does not have a role in determination of the location of the AER.All-trans-retinoic acid (RA) given to pregnant Jc1 : ICR mice at gestation day 12.5 induced various abnormal pad patterns. Cytokinetic analyses with BrdU and the TUNEL method showed that pads were formed by proliferation of mesenchymal cells in the presumptive pad areas. ft was revealed that agenesis of the fibular tarsal pad which was the most frequent type of pad abnormalities was not due to apoptotic cell death but due to reduced cell proliferation. No specific abnormal gene expressions have yet been detected by whole mount in situ hybridization.
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