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1095-564X40712015Nov01Developmental biologyDev BiolGbx2 is essential for maintaining thalamic neuron identity and repressing habenular characters in the developing thalamus.263926-3910.1016/j.ydbio.2015.08.010S0012-1606(15)30123-8The thalamus and habenula, two important nodes of the forebrain circuitry, are derived from a single developmental compartment, called prosomere 2, in the diencephalon. Habenular and thalamic neurons display distinct molecular identity, neurochemistry, and connectivity. Furthermore, their progenitors exhibit distinctive neurogenic patterns with a marked delay in the onset of neurogenesis in the thalamus. However, the progenitors in prosomere 2 express many common developmental regulators and the mechanism underlying the specification and differentiation of these two populations of neurons remains unknown. Gbx2, coding for a homeodomain transcription factor, is initially expressed in thalamic neuronal precursors that have just exited the cell cycle, and its expression is maintained in many mature thalamic neurons in adults. Deletion of Gbx2 severely disrupts histogenesis of the thalamus and abolishes thalamocortical projections in mice. Here, by using genome-wide transcriptional profiling, we show that Gbx2 promotes thalamic but inhibits habenular molecular characters. Remarkably, although Gbx2 is expressed in postmitotic neuronal precursors, deletion of Gbx2 changes gene expression and cell proliferation in dividing progenitors in the developing thalamus. These defects are partially rescued by the mosaic presence of wild-type cells, demonstrating a cell non-autonomous role of Gbx2 in regulating the development of thalamic progenitors. Our results suggest that Gbx2 is essential for the acquisition of the thalamic neuronal identity by repressing habenular identity through a feedback signaling from postmitotic neurons to progenitors.Copyright © 2015 Elsevier Inc. All rights reserved.MallikaChatterjeeCDepartment of Genetics and Genome Sciences, University of Connecticut School of Medicine, 400 Farmington Avenue, Farmington, CT 06030-6403, United States.GuoQiuxiaQDepartment of Genetics and Genome Sciences, University of Connecticut School of Medicine, 400 Farmington Avenue, Farmington, CT 06030-6403, United States.LiJames Y HJYDepartment of Genetics and Genome Sciences, University of Connecticut School of Medicine, 400 Farmington Avenue, Farmington, CT 06030-6403, United States. Electronic address: jali@uchc.edu.engR01 MH094914MHNIMH NIH HHSUnited StatesR01MH094914MHNIMH NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., Extramural20150820
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