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The Journal of Neuroscience, November 19, 2003, 23(33):10613-10621

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Development/Plasticity/Repair
Dynamic Expression of RGS4 in the Developing Nervous System and Regulation by the Neural Type-Specific Transcription Factor Phox2b

Nicolas Grillet, Véronique Dubreuil, Héloïse D. Dufour, and Jean-François Brunet

Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8542, Département de Biologie, Ecole Normale Supérieure, 75005 Paris, France

Previous studies have shown that members of the family of regulators of G-protein signaling (RGS), including RGS4, have a discrete expression pattern in the adult brain (Gold et al., 1997). Here, we describe for RGS4 a distinct, mostly transient phase of neuronal expression, during embryonic development: transcription of RGS4 occurs in a highly dynamic manner in a small set of peripheral and central neuronal precursors. This expression pattern overlaps extensively with that of the paired-like homeodomain protein Phox2b, a determinant of neuronal identity. In embryos deficient for Phox2b, RGS4 expression is downregulated in the locus coeruleus, sympathetic ganglia, and cranial motor and sensory neurons. Moreover, Phox2b cooperates with the basic helix-loop-helix protein Mash1 to transiently switch on RGS4 after ectopic expression in the chicken spinal cord. Intriguingly, we also identify a heterotrimeric G-protein -subunit, gustducin, as coexpressed with RGS4 in developing facial motor neurons, also under the control of Phox2b. Altogether, these data identify components of the heterotrimeric G-protein signaling pathway as part of the type-specific program of neuronal differentiation.

Key words: RGS; neuronal differentiation; hindbrain; motor neurons; heterotrimeric G-protein; Phox2

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Received May 27, 2003; revised August 29, 2003; accepted September 24, 2003.

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