Retinoid signalling and skeletal development.
Metabolites of vitamin A, including retinoic acid (RA), comprise a class of molecules known to be important in development and homeostasis. RA functions through a class of nuclear hormone receptors, the RA receptors (RARs), to regulate gene transcription. In the developing mammalian limb, RA affects the differentiation of many cell lineages, including those of the chondrogenic lineage. In excess, RA is a potent teratogen, causing characteristic skeletal defects in a stage- and dose-dependent manner. Genetic analysis has shown that the absence of RARs leads to severe deficiencies in cartilage formation at certain anatomical locations while promoting ectopic cartilage formation at other sites. Expression of either a dominant-negative or a weak constitutively active RAR in the developing limbs of transgenic mice adversely affects chondrogenesis leading to skeletal malformations. Together, these results show that RAR-mediated signalling plays a fundamental role in skeletogenesis. This chapter will focus on the function of RARs in regulating chondroblast differentiation and the contribution of RA signalling to appositional and longitudinal growth of the skeletal primordia.
School of Dentistry, Faculty of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1.
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Underhill
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Sampaio
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Weston
D000818:Animals; D001846:Bone Development / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology; D001842:Bone and Bones / Q000002:abnormalities*; D020219:Chondrogenesis / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D017880:Limb Deformities, Congenital / Q000196:embryology / Q000235:genetics / Q000503:physiopathology; D010012:Osteogenesis / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000502:physiology*; D047488:Retinoid X Receptors; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors