The tail of the frog tadpole, comprising spinal cord, muscle, and notochord, regenerates following partial amputation. We show that, in Xenopus, this occurs throughout development, except for a "refractory period" between stages 45 and 47, when tails heal over without regeneration. Regeneration can be enabled during this refractory period by activation of either the BMP or Notch signaling pathways. Conversely, regeneration can be prevented during the later, regenerative, stages by inhibition of either pathway. BMP signaling will cause regeneration of all tissues, whereas Notch signaling activates regeneration of spinal cord and notochord, but not muscle. An activated form of Msx1 can promote regeneration in the same way as BMP signaling. Epistasis experiments suggest that BMP signaling is upstream of Notch signaling but exerts an independent effect on muscle regeneration. The results demonstrate that regenerative capability can be enabled by genetic modifications that reactivate specific components of the developmental program.

Early in Drosophila embryogenesis, gap gene products directly repress transcription of homeotic (HOX) genes and thereby delimit HOX expression domains. Subsequently, Polycomb-group proteins maintain this repression. Currently, there is no known molecular link between gap and Polycomb-group proteins. Here, dMi-2 is identified as a protein that binds to a domain in the gap protein Hunchback that is specifically required for the repression of HOX genes. Genetic analyses show that dMi-2 participates in both Hunchback and Polycomb repression in vivo. Hence, recruitment of dMi-2 may serve as a link between repression of HOX genes by Hunchback and Polycomb proteins.

FGF-8 has attracted attention particularly because of its importance for limb development in the chick and mouse, although it also has a number of earlier expression domains in these species. We have now cloned an FGF-8 homologue from Xenopus in which it is easier to do functional studies on early development. There is no maternal expression, while zygotic expression is highest in the gastrula and neurula stages. XFGF-8 is expressed as a ring around the blastopore and subsequently in the tail bud. There are several domains in the head including the hatching gland, the branchial clefts, and the midbrain-hindbrain border. At later stages there is a prominent band of expression in the limb bud epidermis. Although there is no morphological apical ridge, this band of expression suggests that the Xenopus limb bud contains a cryptic region with a similar ability to stimulate mesenchymal outgrowth. The mesoderm-inducing activity of XFGF-8 is somewhat lower than that of other FGFs, while the posteriorizing activity is similar. These differences are probably due to the different receptor specificity. The posterior expression and high posteriorizing activity suggest that XFGF-8 contributes to the patterning of the anterior-posterior axis by FGF family members during gastrulation. In contrast to the amniotes, Xenopus limb buds can regenerate following damage. We show that regeneration is correlated with the reexpression of XFGF-8 in the distal epidermis, suggesting that this ability is critical for successful limb regeneration.

Ligand-independent activation of the sevenless receptor tyrosine kinase changes the fate of cells in the developing Drosophila eye Basler, K; Christen, B; Hafen, E Basler, K; Christen, B; Hafen, E. Ligand-independent activation of the sevenless receptor tyrosine kinase changes the fate of cells in the developing Drosophila eye. Cell 1991, 64(6) Ligand-independent activation of the sevenless receptor tyrosine kinase changes the fate of cells in the developing Drosophila eye AbstractCell fate in the developing eye is determined by a cascade of inductive interactions. In this process, the sevenless protein--a receptor tyrosine kinase--is required for the specification of the R7 photoreceptor cell fate. We have constructed a gain-of-function sevenless mutation (SevS11) by overexpressing a truncated sevenless protein in the cells where sevenless is normally expressed. In SevS11 mutant flies, all sevenless-expressing cells initiate neural development. This results in the formation of multiple R7-like photoreceptors per ommatidium. Therefore, sevenless activity appears to be necessary and sufficient for the determination of R7 cell fate. These results illustrate the central role receptor tyrosine kinases can play in the specification of cell fate during development. In this process, the sevenless protein-a receptor tyrosine kinase-is required for the specification of the R7 photoreceptor cell fate. We have constructed a gain-of-function sexenless mutation (SetP) by overexpressing a truncated sevenless proteln in the ceils where sevenless is normally expressed. In Se+ mutant flies, all sevenless-expressing cells initiate neural development. This results in the formation of multiple RFltke photorecep tors perommatidium.Therefore, sevenless activity ap pears to be necessary and sufficient for the determination of R7 cell fate. These results illustrate the central role receptortyrosine klnases can play in the specification of cell fate during development.

Bone morphogenetic protein (BMP) signalling is necessary for both the development of the tail bud and for tail regeneration in Xenopus laevis tadpoles. Using a stable transgenic line in which expression of the soluble BMP inhibitor noggin is under the control of the temperature inducible hsp70 promoter, we have investigated the timing of the requirement for BMP signalling during tail regeneration. If noggin expression is induced followed by partial amputation of the tail, then wound closure and the formation of the neural ampulla occur normally but outgrowth of the regeneration bud is inhibited. Furthermore, we show that BMP signalling is also necessary for limb bud regeneration, which occurs in Xenopus tadpoles prior to differentiation. When noggin expression is induced, limb bud regeneration fails at an early stage and a stump is formed. The situation appears similar to the tail, with formation of the limb bud blastema occurring but renewed outgrowth inhibited. The transcriptional repressor Msx1, a direct target of BMP signalling with known roles in vertebrate appendage regeneration, fails to be re-expressed in both tail and limb in the presence of noggin. DNA labelling studies show that proliferation in the notochord and spinal cord of the tail, and of the blastema in the limb bud, is significantly inhibited by noggin induction, suggesting that in the context of these regenerating appendages BMP is mainly required, directly or indirectly, as a mitogenic factor.