Biomedical subjects

Hilary L Ashe

Publications and source records attributed to Hilary L Ashe.

4 recordsLinked to original sources

PubMed2006

The interpretation of morphogen gradients.

Morphogens act as graded positional cues that control cell fate specification in many developing tissues. This concept, in which a signalling gradient regulates differential gene expression in a concentration-dependent manner, provides a basis for understanding many patterning processes. It also raises several mechanistic issues, such as how responding cells perceive and interpret the concentration-dependent information provided by a morphogen to generate precise patterns of gene expression and cell differentiation in developing tissues. Here, we review recent work on the molecular features of morphogen signalling that facilitate the interpretation of graded signals and attempt to identify some emerging common principles.

Animals↗

PubMed2005

BMP signalling: synergy and feedback create a step gradient.

More than a decade ago, genetic evidence predicted the existence of a Dpp gradient in the early Drosophila embryo. Two recent studies finally reveal Dpp distribution, providing further insights into the mechanism of BMP gradient formation.

Animals↗

PubMed2004

Smad affinity can direct distinct readouts of the embryonic extracellular Dpp gradient in Drosophila.

BACKGROUND: The TGF-beta signaling molecule Decapentaplegic (Dpp) is an essential morphogen that patterns many tissues during Drosophila development, including the embryonic dorsal ectoderm and larval wing imaginal disk. An activity gradient of Dpp specifies distinct cell fates in the dorsal ectoderm of the embryo through the activation of different transcriptional threshold responses. RESULTS: We have analyzed the gene Race, which is expressed in response to peak levels of Dpp signaling in gastrulating embryos. We show that the Smad transcription factors, which are intracellular transducers of Dpp signaling, are essential activators of Race in vivo. Furthermore, increasing the affinity of the Smad binding sites in the Race enhancer broadens the expression pattern of a linked reporter gene and alters its behavior in mutant embryos to that characteristic of a distinct threshold response. CONCLUSIONS: Smad activator affinity is a critical determinant of the threshold response to the extracellular Dpp gradient in the embryo. Our results identify a mechanism for interpreting the Dpp gradient in the embryo which is different to the reciprocal repressor gradient model proposed for the wing disk. We suggest that transcription factor binding site affinity will be a general strategy used in the interpretation of other extracellular morphogen gradients.

Animals↗

PubMed2002

BMP signalling: visualisation of the Sog protein gradient.

Extracellular inhibitors are commonly used in development to modulate the activities of signalling molecules. Direct visualisation in the Drosophila embryo of Sog, a Dpp/Scw inhibitor, has now revealed a graded distribution established by degradation and endocytosis.

Animals↗