The role of the apical ridge of ectoderm in the differentiation of the morphological structure and inductive specificity of limb parts in the chick

Saunders, John W.; Cairns, John M.; Gasseling, Mary T.

doi:10.1002/jmor.1051010104

Cited by 121 publications

(23 citation statements)

References 15 publications

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“…They have further shown that the more advanced the blastema is at the time of transplantation, the more distally complete is the resulting regenerate. These results are comparable to those obtained in developing amphibian limbs (Tschumi, 1957) and chick limbs (Saunders, 1948;Saunders et al, 1957) and show that, during vertebrate limb morphogenesis, the capacity,for differentiation of limb structures is acquired in a proximal-distal sequence over time. However, a major difference exists between developing and regenerating limbs.…”

Section: Introductionsupporting

confidence: 87%

The interaction between the blastema and stump in the establishment of the anterior-posterior and proximal-distal organization of the limb regenerate

Iten

Bryant

1975

Developmental Biology

137

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Section: Introductionsupporting

confidence: 87%

The interaction between the blastema and stump in the establishment of the anterior-posterior and proximal-distal organization of the limb regenerate

Iten

Bryant

1975

Developmental Biology

137

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“…Developmentally, the localization of PCD in the UPE could serve two important functions. First, the removal of the UPE by PCD could modulate levels of Fgf8 expression, providing a signal for differentiation to occur; a similar use of PCD is seen in the developing limb, where removal of the AER reduces Fgf8 signaling to stimulate differentiation of the underlying mesenchyme (Zwilling, 1955;Saunders et al, 1957;Macias et al, 1997;Niswander et al, 1994). Second, to achieve closure of the urethra, the progressing mesenchyme must cover the medial epithelial layer.…”

Section: Discussionmentioning

confidence: 99%

Loss of Bmp7 and Fgf8 signaling in Hoxa13-mutant mice causes hypospadia

et al. 2003

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In humans and mice, mutations in Hoxa13 cause malformation of limb and genitourinary (GU) regions. In males, one of the most common GU malformations associated with loss of Hoxa13 function is hypospadia,a condition defined by the poor growth and closure of the urethra and glans penis. By examining early signaling in the developing mouse genital tubercle,we show that Hoxa13 is essential for normal expression of Fgf8 and Bmp7 in the urethral plate epithelium. In Hoxa13GFP-mutant mice, hypospadias occur as a result of the combined loss of Fgf8 and Bmp7 expression in the urethral plate epithelium, as well as the ectopic expression of noggin(Nog) in the flanking mesenchyme. In vitro supplementation with Fgf8 restored proliferation in homozygous mutants to wild-type levels, suggesting that Fgf8 is sufficient to direct early proliferation of the developing genital tubercle. However, the closure defects of the distal urethra and glans can be attributed to a loss of apoptosis in the urethra,which is consistent with reduced Bmp7 expression in this region. Mice mutant for Hoxa13 also exhibit changes in androgen receptor expression, providing a developmental link between Hoxa13-associated hypospadias and those produced by antagonists to androgen signaling. Finally,a novel role for Hoxa13 in the vascularization of the glans penis is also identified.

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“…However, the results of our experiments in the chick and mouse do not support a model in which Tbx5 is involved in directing migration of cells of the prospective forelimb. In higher vertebrates, cells of the prospective forelimb do not undergo a similar migration (Saunders et al, 1957;Saunders et al, 1959;Searls, 1967;Searls and Janners, 1969) and Tbx5-expressing cells detected in the prospective forelimb region are not migratory (Gibson-Brown et al, 1998;Isaac et al, 1998;Ohuchi et al, 1998). Somite-derived cells that contribute to the limb do not express Tbx5 (data not shown).…”

Section: Tbx5 Is Required For Forelimb Bud Developmentmentioning

confidence: 99%

Tbx5 is required for forelimb bud formation and continued outgrowth

Rallis¹,

Bruneau

Buono³

et al. 2003

Development

215

255

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Tbx5 is a T-box transcription factor expressed exclusively in the developing forelimb but not in the developing hindlimb of vertebrates. Tbx5 is first detected in the prospective forelimb mesenchyme prior to overt limb bud outgrowth and its expression is maintained throughout later limb development stages. Direct evidence for a role of Tbx5 in forelimb development was provided by the discovery that mutations in human TBX5 cause Holt-Oram Syndrome (HOS), a dominant disorder characterised predominantly by upper(fore) limb defects and heart abnormalities. Misexpression studies in the chick have demonstrated a role for this gene in limb-type specification. Using a conditional knockout strategy in the mouse to delete Tbx5 gene function in the developing forelimb, we demonstrate that this gene is also required at early limb bud stages for forelimb bud development. In addition, by misexpressing dominant-negative and dominant-activated forms of Tbx5 in the chick wing we provide evidence that this gene is also required at later stages of limb bud development for continued limb outgrowth. Our results provide a context to understand the defects observed in HOS caused by haploinsufficiency of TBX5 in human. Moreover, our results also demonstrate that limb bud outgrowth and specification of limb identity are linked by a requirement for Tbx5.

show abstract

The role of the apical ridge of ectoderm in the differentiation of the morphological structure and inductive specificity of limb parts in the chick

Cited by 121 publications

References 15 publications

The interaction between the blastema and stump in the establishment of the anterior-posterior and proximal-distal organization of the limb regenerate

The interaction between the blastema and stump in the establishment of the anterior-posterior and proximal-distal organization of the limb regenerate

Loss of Bmp7 and Fgf8 signaling in Hoxa13-mutant mice causes hypospadia

Tbx5 is required for forelimb bud formation and continued outgrowth

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