The transformation suppressor gene Reck is required for postaxial patterning in mouse forelimbs
نویسندگان
چکیده
The membrane-anchored metalloproteinase-regulator RECK has been characterized as a tumor suppressor. Here we report that mice with reduced Reck-expression show limb abnormalities including right-dominant, forelimb-specific defects in postaxial skeletal elements. The forelimb buds of low-Reck mutants have an altered dorsal ectoderm with reduced Wnt7a and Igf2 expression, and hypotrophy in two signaling centers (i.e., ZPA and AER) that are essential for limb outgrowth and patterning. Reck is abundantly expressed in the anterior mesenchyme in normal limb buds; mesenchyme-specific Reck inactivation recapitulates the low-Reck phenotype; and some teratogens downregulate Reck in mesenchymal cells. Our findings illustrate a role for Reck in the mesenchymal-epithelial interactions essential for mammalian development.
منابع مشابه
Oncogene-mediated downregulation of RECK, a novel transformation suppressor gene.
The RECK gene was initially isolated as a transformation suppressor gene encoding a novel membrane-anchored glycoprotein and later found to suppress tumor invasion and metastasis by regulating matrix metalloproteinase-9. Its expression is ubiquitous in normal tissues, but undetectable in many tumor cell lines and in fibroblastic lines transformed by various oncogenes. The RECK gene promoter has...
متن کاملPostaxial polydactyly in forelimbs of CRABP-II mutant mice.
The cytoplasmic retinoic acid (RA)-binding protein CRABP-II is expressed widely throughout early morphogenesis in mouse embryo, but its expression becomes more restricted as organogenesis progresses. CRABP-II expression remains strong in the developing limb bud suggesting a role for this protein in limb patterning. Here, we show that the CRABP-II promoter can direct expression of a lacZ transge...
متن کاملCritical roles for murine Reck in the regulation of vascular patterning and stabilization
Extracellular matrix (ECM) is known to play several important roles in vascular development, although the molecular mechanisms behind these remain largely unknown. RECK, a tumor suppressor downregulated in a wide variety of cancers, encodes a membrane-anchored matrix-metalloproteinaseregulator. Mice lacking functional Reck die in utero, demonstrating its importance for mammalian embryogenesis; ...
متن کاملCorrigendum: Critical roles for murine Reck in the regulation of vascular patterning and stabilization.
Extracellular matrix (ECM) is known to play several important roles in vascular development, although the molecular mechanisms behind these remain largely unknown. RECK, a tumor suppressor downregulated in a wide variety of cancers, encodes a membrane-anchored matrix-metalloproteinase-regulator. Mice lacking functional Reck die in utero, demonstrating its importance for mammalian embryogenesis;...
متن کاملA novel screen using the Reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs
The membrane-anchored matrix metalloproteinase-regulator RECK is often downregulated in various types of cancers; the levels of residual RECK in resected tumors often correlate with better prognosis. Forced expression of RECK in cancer cells suppresses tumor angiogenesis, invasion, and metastasis in xenograft models. RECK is therefore a promising marker for benignancy and a potential effector i...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 1 شماره
صفحات -
تاریخ انتشار 2012