Lhx2 and Lhx9 Determine Neuronal Differentiation and Compartition in the Caudal Forebrain by Regulating Wnt Signaling

Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Karlsruhe, Germany.
PLoS Biology (Impact Factor: 11.77). 12/2011; 9(12):e1001218. DOI: 10.1371/journal.pbio.1001218
Source: PubMed

ABSTRACT Author Summary
The thalamus is the interface between the body and the brain. It connects sensory organs with higher brain areas and modulates processes such as sleep, alertness, and consciousness. Our knowledge about the embryonic development of this central relay station is still fragmented. Here, we show that the transcription factors Lhx2 and Lhx9 are essential for the development of the relay thalamus. Zebrafish embryos lacking Lhx2/Lhx9 have stalled neurogenesis - neuronal progenitor cells accumulate but do not complete their differentiation into thalamic neurons. In addition, we find that the neighboring Wnt-expressing epithalamus expands into the space containing mis-specified thalamus in these embryos. We identified a thalamus-specific cell adhesion modulator, Pcdh10b, which is controlled by canonical Wnt signaling. Altered Wnt-dependent Pcdh10b function in Lhx2/Lhx9-deficient embryos leads to intermingling of the thalamus and adjacent brain compartments and consequently regionalization within the caudal forebrain is lost. Organization of the developing CNS into molecularly distinct but transient segments and the implications for regional differentiation are well established for the developing hindbrain. We conclude that this applies to caudal forebrain too: Lhx2 and Lhx9 emerge as crucial factors driving neurogenesis and maintaining the regional integrity of the caudal forebrain. These are two prerequisites for the formation of this important relay station in the brain.

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