An Hh-dependent Pathway in Lateral Plate Mesoderm Enables the Generation of Left/right Asymmetry

Overview

Journal Curr Biol

Publisher Cell Press

Specialty Biology

Date 2009 Nov 3

PMID 19879143

Citations 28

Authors

Charisios D Tsiairis

Andrew P McMahon

Affiliations

Soon will be listed here.

Abstract

Breaking bilateral symmetry is critical for vertebrate morphogenesis. In the mouse, directional looping of the heart and rotation of the embryo, the first overt evidence of left/right asymmetry (L/R), are observed at early somite stages ( approximately E8.5) [1, 2]. Activation of a Nodal-Pitx2 regulatory pathway specifically within the left lateral plate mesoderm (LPM) is critical for these events [3-10]. Asymmetric expression of Nodal is thought to be triggered by left-oriented, cilia-generated flow within the ventral, midline node [11, 12]. Genetic removal of Hedgehog (Hh) signaling in the mouse demonstrates a requirement for Hedgehog signals in the symmetry-breaking process [13], and analysis of node trafficking has suggested a mechanism of directional transport in the node that might relate to symmetry breaking in the LPM [14]. Here we provide evidence that Hedgehog signaling in the node is not essential for breaking bilateral symmetry. In contrast, direct Hh signaling in the LPM is critical. Evidence is presented that Sonic and Indian hedgehog signals act together, through a Foxf1/Bmp4 pathway, to enable the initiation and propagation of Nodal signaling within the LPM, regulating the competence of that tissue to respond to the Nodal pathway.

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