The effects of retinoids on cartilage differentiation in micromass cultures of chick facial primordia and the relationship to a specific facial defect

Wedden, Sarah; Lewin-Smith, Michael R.; Tickle, C.

doi:10.1016/0012-1606(87)90334-4

Cited by 29 publications

(10 citation statements)

References 15 publications

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“…This effect was shown to be most pronounced in cells derived from the more proximal limb bud indicating that the late blastemal stage of chondrogenesis is most vulnerable to RA treatment (43). In vivo, low doses are reported to enhance chondrogenesis, whereas high doses result in inhibition of cartilage formation (44,45). Loss of RA receptor-mediated signaling was shown to be necessary and sufficient for expression of the chondroblast phenotype (46).…”

Section: Discussionmentioning

confidence: 99%

Mutant Hoxd13 induces extra digits in a mouse model of synpolydactyly directly and by decreasing retinoic acid synthesis

et al. 2008

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Individuals with the birth defect synpolydactyly (SPD) have 1 or more digit duplicated and 2 or more digits fused together. One form of SPD is caused by polyalanine expansions in homeobox d13 (Hoxd13). Here we have used the naturally occurring mouse mutant that has the same mutation, the SPD homolog (Spdh) allele, and a similar phenotype, to investigate the molecular pathogenesis of SPD. A transgenic approach and crossing experiments showed that the Spdh allele is a combination of loss and gain of function. Here we identify retinaldehyde dehydrogenase 2 (Raldh2), the rate-limiting enzyme for retinoic acid (RA) synthesis in the limb, as a direct Hoxd13 target and show decreased RA production in limbs from Spdh/Spdh mice. Intrauterine treatment with RA restored pentadactyly in Spdh/Spdh mice. We further show that RA and WT Hoxd13 suppress chondrogenesis in mesenchymal progenitor cells, whereas Hoxd13 encoded by Spdh promotes cartilage formation in primary cells isolated from Spdh/Spdh limbs, and that this was associated with increased expression of Sox6/9. Increased Sox9 expression and ectopic cartilage formation in the interdigital mesenchyme of limbs from Spdh/Spdh mice suggest uncontrolled differentiation of these cells into the chondrocytic lineage. Thus, we propose that mutated Hoxd13 causes polydactyly in SPD by inducing extraneous interdigital chondrogenesis, both directly and indirectly, via a reduction in RA levels.

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Section: Discussionmentioning

confidence: 99%

Mutant Hoxd13 induces extra digits in a mouse model of synpolydactyly directly and by decreasing retinoic acid synthesis

et al. 2008

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“…Neural crest cells from distinct anteroposterior levels express different combinations of homeobox transcription factors [61], which could influence the response of downstream genes to the nuclear targets of phosphorylated ERK. The frontonasal and mandibular mesenchyme also exhibit distinct responses to retinoic acid, a teratogenic vitamin A derivative, with respect to both their in vivo morphogenesis and in vitro chondrogenic differentiation [62][63][64]. Retinoids influence multiple genes involved in skeletal differentiation and craniofacial patterning, including genes for homeobox transcription factors, by activating nuclear receptors of the RAR and RXR classes [65,66].…”

Section: Discussionmentioning

confidence: 99%

MEK-ERK signaling plays diverse roles in the regulation of facial chondrogenesis

Bobick

Kulyk

2006

Experimental Cell Research

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“…Beak defects were often seen in ta2 embryos which received more than 0.1 mg/ml of retinoic acid. This was also observed in normal, control embryos which were treated with retinoic acid (see Wedden, 1987;Wedden et al, 1987). Normal control embryos which had retinoic acidsoaked beads implanted anteriorly displayed skeletal patterns ranging from an extra digit 2 to the pattern 4-3-3-4, depending upon the concentration of retinoic acid administered (Fig.…”

Section: Normal Polarizing Zone Grafted To Talpid2 (Fig 5 )mentioning

confidence: 65%

The talpid² chick limb has weak polarizing activity and can respond to retinoic acid and polarizing zone signal

Dvorak

Fallon

1992

Developmental Dynamics

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The tuZpi8 @a2) chick mutant has wide, polydactylous wings and legs. TuZpid2 limb cartilages have abnormal morphology and a very subtle anteroposterior polarity. Specifically, posterior ta2 limb structures are identifiable, while more anterior cartilages are less distinctive. Here, we investigate the development of anteroposterior limb pattern in the tu2 embryo. We show that tu2 posterior limb bud mesoderm is capable of respecifying the anteroposterior axis of a normal wing. However, the average duplication obtained after grafting a tu2 polarizing region was significantly less than the average duplication formed after a graft of normal wing bud polarizing zone. Thus, polarizing activity appears to be weak in tu2. Grafts of normal polarizing zone to the posterior edge of tu2 wing buds had no effect on the tu2 phenotype. This result suggests that a weakly functioning polarizing signal does not account for the altered anteroposterior polarity in tu2 limbs, and that normal polarizing zone activity is not sufficient for formation of normal limb bud cartilages. We demonstrated that transmission of a polarizing signal through the tu2 limb mesoderm was normal. In addition, tu2 anterior border mesoderm had no polarizing activity. We also assessed the ability of tu2 limb bud mesoderm to respond to a polarizing signal. Either normal polarizing zone tissue or a bead containing retinoic acid was placed at the anterior edge of tu2 wing buds at stages 18-23. Both polarizing zone and retinoic acid caused respecification of the tu2 wing anteroposterior axis. The result was that a tu2 ulna replaced the radius, and the most posterior digit was duplicated anteriorly. Limb cartilages with normal morphology never formed. When a bead containing retinoic acid was placed at the posterior edge of tu2 wing buds, there was no effect on anteroposterior pattern. However, beads with retinoic acid always caused a reduction in the number of tu2 wing digits which formed, whether the beads were placed at the anterior or posterior edge of the developing tu2 limb.

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The effects of retinoids on cartilage differentiation in micromass cultures of chick facial primordia and the relationship to a specific facial defect

Cited by 29 publications

References 15 publications

Mutant Hoxd13 induces extra digits in a mouse model of synpolydactyly directly and by decreasing retinoic acid synthesis

Mutant Hoxd13 induces extra digits in a mouse model of synpolydactyly directly and by decreasing retinoic acid synthesis

MEK-ERK signaling plays diverse roles in the regulation of facial chondrogenesis

The talpid² chick limb has weak polarizing activity and can respond to retinoic acid and polarizing zone signal

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The effects of retinoids on cartilage differentiation in micromass cultures of chick facial primordia and the relationship to a specific facial defect

Cited by 29 publications

References 15 publications

Mutant Hoxd13 induces extra digits in a mouse model of synpolydactyly directly and by decreasing retinoic acid synthesis

Mutant Hoxd13 induces extra digits in a mouse model of synpolydactyly directly and by decreasing retinoic acid synthesis

MEK-ERK signaling plays diverse roles in the regulation of facial chondrogenesis

The talpid2 chick limb has weak polarizing activity and can respond to retinoic acid and polarizing zone signal

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The talpid² chick limb has weak polarizing activity and can respond to retinoic acid and polarizing zone signal