James Briscoe

The Gene Regulatory Logic of Sonic Hedgehog Morphogen Pattern Formation

Gradients of diffusible signals, normally referred to as morphogens, govern patterns of gene expression in many developing tissues. In the vertebrate neural tube, for example, molecularly distinct domains of progenitors that generate different neuronal subtypes are arrayed along the dorsal-ventral axis. We are particularly interested in the ventral part of the neural tube, which generates the motor neurons and interneurons that coordinate motor output. Here pattern formation is governed by the morphogen Sonic Hedgehog (Shh). We have found

that both the concentration and duration of Shh signalling contributes to pattern formation by regulating a set of downstream transcription factors. The design of the transcriptional network integrates the activity of the morphogen effectors with uniformly expressed and differentially regulated transcription factors and is responsible for the spatial-temporal patterns of gene expression. In addition, the network renders cells insensitive to fluctuations in signaling and confers hysteresis – memory of the signal. Together, the interplay between the input by Shh and the transcriptional network of recipient progenitor cells explain the stereotyped and precise patterning of the developing neural tube.
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