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Presenting Author(s) Sheila Bell
Abstract Title Sp8 is required for AER formation.
Full author List Sheila Bell, Claire Schreiner, Jun Ma, and William Scott
Text of abstract

Sp8 is an evolutionarily conserved zinc finger transcription factor that plays a crucial role in appendage outgrowth in vertebrates and invertebrates. In the mouse, Sp8 is normally expressed throughout the emerging limb ectoderm including the AER precursors/ mature AER. Diminished Sp8 expression is observed in limb buds of the transgene insertional mutant legless. Insertion of the legless transgene >80kb upstream of the Sp8 gene, created a hypomorphic Sp8 allele. Targeted deletion of Sp8 results in the absence of forelimb and hindlimb structures distal to the stylopod. Although AER formation is initiated in Sp8-/- limb buds, the AER precursors fail to accumulate at the limb bud apex and the expression of Fgf8, En1, Dlx2, Bmp4 and other marker genes ceases.

We have performed an Affymetrix chip array experiment using Sp8 mutant and wildtype stage 1 hindlimb bud ectoderm samples and identified two putative modulators of the Wnt signaling pathway as downstream targets. One of these is the Wnt antagonist Dkk4 and the other is the candidate gene for the footless transgene insertional mutation, Ftl. Expression of Ftl and Dkk4 is restricted to the AER precursors. Evidence linking the Ftl candidate gene to the WNT signalling pathway is the severe limb truncation phenotype observed when the Ftl mutation is mated onto a transgenic line creating nulls of the Wnt-co-receptor Lrp6. Studies are underway to determine if Sp8 can directly regulate transcription of the Ftl and Dkk4 promoters.

Which session is your work most relevant to: Limb initiation