Fig. 1. Morphogen gradients pattern developing tissues. (A) Theoretical morphogen gradient. A gradient of a signalling molecule (blue) within tissue (grey cells) provides positional information, instructing cells to adopt distinct cell fates (coloured cells), according to the concentration of signal to which they are exposed. (B) The graded distribution of the transcription factor Bicoid establishes anteroposterior (AP) polarity in the developing Drosophila embryo. Immunostaining reveals the gradient of Bicoid distribution in the embryo. Expression of orthodenticle and hunchback genes are induced by high and low levels of Bicoid, respectively. (C) The dorsoventral (DV) axis of the early Drosophila embryo is patterned by graded Dorsal (Dl) activity (left). The ligand Spatzle binding to its transmembrane (TM) receptor Toll initiates signal transduction that, through the action of the kinase Pelle, activates the NF-B-like transcription factor Dl. (Right) Graded distribution of Dl protein; twist and rhomboid are induced by high and low levels of Dl, respectively. (D) In both Drosophila and vertebrates, Dpp/BMP signalling operates in a graded manner to pattern several developing tissues. A Dpp/Screw (Scw) heterodimer activates its heteromeric complex containing receptor TM serine/threonine kinases. The activated receptor phosphorylates Mad/Smad transcription factors that, with Med/Smad4 transcription factor, then translocate to the nucleus where they can activate, in combination with other proteins, target gene expression. In the Drosophila embryo, high Dpp levels are distributed along the dorsal midline (top panel), resulting in a peak of phosphorylated Mad (pMad) (middle panel) and the induction of target genes such as Race (bottom panel). In the Drosophila embryo, a stepped distribution of Dpp is observed, resulting in a stepped activation of Mad (see text for details). (E) Graded Sonic hedgehog (Shh) signalling patterns the ventral neural tube. In the absence of Shh ligand, the TM protein Patched (Ptch) inhibits Smoothened (Smo), consequently Gli factors are converted to transcriptional repressors (GliR). Shh binds to Ptch, relieving repression of Smo, which signals to block the production of GliR proteins, promoting the generation of Gli activators (GliA). (Right) A Shh gradient can be visualised in the ventral neural tube (top panel), which regulates homeodomain protein expression (bottom panel). (B) Reproduced, with permission, from Ochoa-Espinosa et al. (Ochoa-Espinosa et al., 2005) (Bicoid protein) and Ephrussi and St Johnston (Ephrussi and St Johnston, 2004) (orthodenticle and hunchback mRNAs). (C) Reproduced, with permission, from Rushlow et al. (Rushlow et al., 1989) (Dl protein); Berkeley Drosophila Genome Project In Situ Database (http://www.fruitfly.org/cgi-bin/ex/insitu.pl) (twist); and Erives and Levine (Erives and Levine, 2004) (rhomboid neuroectoderm enhancer directed lacZ expression). (D) Reproduced with permission from Shimmi et al. (Shimmi et al., 2005) (Dpp-HA); Wang and Ferguson (Wang and Ferguson, 2005) (pMad); and Wharton et al. (Wharton et al., 2004) (Race). (E, Shh gradient) Reproduced, with permission, from Gritli-Linde et al. (Gritli-Linde et al., 2001).