A homeodomain feedback circuit underlies step-function interpretation of a Shh morphogen gradient during ventral neural patterning

• DOI: 10.1242/dev.054288
• Publication Date: 2010-11-09T12:33:10Z
• Authors: Madelen Lek; José M. Dias; Ulrika Marklund; Christopher W. Uhde; Sanja Kurdija; Qiubo Lei; Lori Sussel; John L. Rubenstein; Michael P. Matise; Hans-Henning Arnold; Thomas M. Jessell; Johan Ericson
• Keywords: Morphogen

The deployment of morphogen gradients is a core strategy to establish cell diversity in developing tissues, but little known about how small differences the concentration extracellular signals are translated into robust patterning output responding cells. We have examined activity homeodomain proteins, which presumed operate downstream graded Shh signaling neural patterning, and describe feedback circuit between pathway transcription factors that establishes non-graded regulation activity. Nkx2 proteins intrinsically strengthen responses feed-forward amplification required for ventral floor plate p3 progenitor fates. Conversely, Pax6 has an opposing function antagonize signaling, provides intrinsic resistance important constrain inductive capacity gradient over time. Our data further suggest cells progenitors gated by temporal switch neuronal potential, rather than different concentrations. These dynamic, changes essential interpretation, provide rationale explain mechanistically phenomenon cellular memory exposure.