Yanick Botilde(個体機能学講座 発生遺伝学研究室(濱田研究室))

演題 From signal to response: generating neural diversity in the mammalian central nervous system
演者 Prof. Andrew McMahon
(Department of Molecular and Cellular Biology, Harvard University)

2009年 6月4日(木) 15:30-16:00

場所 吹田キャンパス ナノバイオロジー棟 3階セミナー室



During development of central nervous system, neural tube is patterned along both anteroposterior and dorsoventral axes, involving many signallings (Retinoic acid, FGF, Wnt,...)

Among these wide ranges of signalling, Dr. McMahon and his team are particularly focusing on Sonic Hedgehog (Shh) signalling and the dynamic regulatory network leading to neural tube pattern. Shh, initially produced at the notochord level generates a gradient along Dorsoventral axis of neural tube, this leading to the specification of different interneurons (V0, V1, V2 and V3) and motoneurons precursors in a Shh concentration-dependant pattern. 

The amount of Shh required for a proper differentiation at long term, or how to induce a robust response from an initiation signal even at low concentration appear to involve membrane receptors BOC/CDO/Gas-1, able to enhance the response to Shh. Moreover, the genes encoding for these receptors are downregulated by Shh.

A triple Knock-out of these specific genes completely unpairs Shh signalling in neural tube, and dorsalization phenotype, as seen bye the absence of ventral neurons marker (Nkx2.2,)
Moreover a positive feedback is done by Ptch1 and Hhip1, as a more ventralized neural tube can be seen in their absence (Expression of ventral marker Nkx6.1 is dorsally expanded despite a normal Shh concentration gradient)
In brief, Ptch1 and Hhip1 attenuate the response and decrease the range of Shh signalling, while BOC, CDO and Gas-1 extend the response and enhance the range of signalling.

But further studies are now required to understand the integration of the numerous parameters involved, such as evolution of Shh signalling through development time and others signalling required for proper patterning (Wnt, Retinoic Acid, FGF, Notch,...).