Roles for FGF8 in the Induction, Initiation, and Maintenance of Chick Limb Development

Point mutations in the intronic ZRS region of Lmbr1, a limb specific cis-regulatory element of Sonic hedgehog (Shh), are associated with polydactyly in humans, cats, and mice. We and others have recently mapped the dominant preaxial polydactyly (Po) locus in Silkie chickens to a single nucleotide polymorphism (SNP) in the ZRS region. Using polymorphisms in the chicken Shh sequence, we confirm that the ZRS region directly regulates Shh expression in the developing limb causing ectopic Shh expression in the anterior leg, prolonged Shh expression in the posterior limb, and allelic imbalance between wt and Slk Shh alleles in heterozygote limbs. Using Silkie legs, we have explored the consequences of increased Shh expression in the posterior leg on the patterning of the toes, and the induction of preaxial polydactyly.

“…Probes were made from the following templates: Fgf4 (Niswander et al, 1994), Fgf8 (Crossley et al, 1996), Gli1, Gli2 (Marigo et al, 1996a), Gremlin (Merino et al, 1999) …”

Section: Wholemount Rna In Situ Hybridisationmentioning

confidence: 99%

The chicken polydactyly (Po) locus causes allelic imbalance and ectopic expression of Shh during limb development

Dunn

Paton

Clelland

et al. 2011

“…During normal limb development Fgf8 expression is detected in the surface ectoderm of the forelimb from embryonic day (E) 9 onwards (17 Somites; Sun et al, 2002). Expression is first detected in the ventral ectoderm, where the precursors of the AER originate, and later in the mature AER located at the distal dorsoventral boundary (Crossley et al, 1996). In Fgf8 flox/d2,3 ;Mox2 Cre/ϩ embryos (hereafter termed Mox2Cre; Fgf8), Fgf8 expression should have been inactivated in the surface ectoderm prior to limb bud emergence.…”

Section: Targeted Deletion Of Fgf8 In the Prelimb Ectoderm Using The mentioning

confidence: 99%

“…Fgf4, 8, 9, and 17 are expressed in AER cells, in a similar pattern in mouse and in chick. Of these, Fgf8 is always expressed by AER cells, from their initial specification as AER precursors until the final regression of the AER (Crossley et al, 1996). For this reason, Fgf8 is considered the best marker of the AER (Crossley and Martin, 1995;Mahmood et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

The incomplete inactivation of Fgf8 in the limb ectoderm affects the morphogenesis of the anterior autopod through BMP‐mediated cell death

Delgado

Domínguez-Frutos

Schimmang

et al. 2008

Here we analyze limb development after the conditional inactivation of Fgf8 from the epiblast, using the previously described MORE (Mox2Cre) line. This line drives variable mosaic recombination of a floxed Fgf8 allele, resulting in a small proportion of AER cells that maintain Fgf8 expression. The phenotype of Mox2Cre;Fgf8 limbs is most similar to that of Msx2Cre;Fgf8 forelimbs, indicating that a small but durable expression of FGF8 is equivalent to an early normal, but transitory, expression. This functional equivalence likely relies on the subsequent Fgf4 upregulation that buffers the differences in the pattern of Fgf8 expression between the two conditional mutants. The molecular analysis of Mox2Cre;Fgf8 limbs shows that, despite Fgf4 upregulation, they develop under reduced FGF signaling. These limbs also exhibit an abnormal area of cell death at the anterior forelimb autopod, overlapping with an ectopic domain of Bmp7 expression, which can explain the abnormal morphogenesis of the anterior autopod. Developmental Dynamics 237: 649 -658, 2008.

“…These mechanisms are considered to be shared among gnathostome vertebrates. The flank region between the forelimb and hindlimb is competent to form additional limbs in response to FGFs (Cohn et al, 1995;Crossley et al, 1996;Yonei-Tamura et al, 1999 [chick]; Tanaka et al, 2000 [mouse]; Abe et al, 2007 [zebrafish]; YoneiTamura et al, 2008 [cartilaginous fish] and references therein). However, despite their potential to form additional limbs in the flank, a gnathostome species with a third set of paired limbs has never emerged.…”

Section: Introductionmentioning

confidence: 99%

Role of paraxial mesoderm in limb/flank regionalization of the trunk lateral plate

Noro

Yuguchi

Sato

et al. 2011

To understand the developmental mechanism that determines limb size and the consequent limb-to-trunk proportions in the tetrapod body, we investigated the role of the paraxial mesoderm in the specification of the limb and flank fields in the chick embryo. We found that the paraxial mesoderm subjacent to the limb field can affect the size of the limb bud along the anterior-posterior and proximal-distal axes. We also found that the paraxial mesoderm subjacent to the flank plays roles in suppressing the emergence and growth of the limb bud and in promoting flank-specific apoptosis in the lateral plate mesoderm. Our results suggest that signals from the paraxial mesoderm specify the limb and flank fields in the competent lateral plate mesoderm.