Transcriptional cascades responsible for initiating the formation of vertebrate embryonic structures

The development of vertebrate limbs is an excellent model to study patterning and growth regulation in embryogenesis (Capdevila and Izpisua Belmonte, 2001; Johnson and Tabin, 1997). The limb buds that result in morphologically distinct forelimbs and hindlimbs arise from the lateral plate mesoderm (LPM) at precise locations along the anteroposterior (AP) axis of the embryo. The induction of limb buds at specific locations along the AP axis implies the localized expression of an inductive or competence factor. However, the initial steps in limb bud outgrowth from these fields of patterned LPM and the signals that initiate limb bud outgrowth are not known. The definition of the fields of LPM that will give rise to limb buds occur possibly as a result of patterning by Hox gene activity along the AP axis of the vertebrate embryo (Cohn et al., 1997; Cohn and Tickle, 1999; Popperl et al., 2000; Rancourt et al., 1995), but it not known what signals are established by these patterning events that lead to limb bud outgrowth. Experiments in chicken embryos have suggested that fibroblast growth factors (FGFs) or other molecules secreted from the intermediate mesoderm (IM), which will give rise to the nephrogenic mesenchyme (NM), may be responsible for initiating limb outgrowth (reviewed by Martin, 1998). These signals are thought to initiate expression of Fgf10, which is required for limb bud outgrowth, in the limb field mesenchyme (Min et al., 1998; Sekine et al., 1999). FGF10 in turn activates Fgf8 expression in the ectoderm overlying the limb field mesoderm (Min et al., 1998; Ohuchi et al., 1997; Sekine et al., 1999). FGF8 and other FGFs secreted from the apical ectodermal ridge (AER) subsequently promote limb bud outgrowth, in part by maintaining Fgf10 expression (Crossley et al., 1996; Lewandoski et al., 2000; Moon and Capecchi, 2000; Ohuchi et al., 1997; Sun et al., 2002; Vogel et al., 1996; Xu et al., 1998). FGFs are expressed in the IM and LPM along the entire length of the embryo, so it follows that there must be a 623 Development 130, 623-633 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00191