Abstract
Unlike the laminar arrangement of neurons in the neocortex, thalamic neurons aggregate to form about dozens of nuclei, many of which make topographic connections with specific areas in the neocortex. The molecular mechanisms underlying the formation of thalamic nuclei remain largely unknown. Homeodomain transcription factor Gbx2 is specifically expressed in the developing thalamus. Deleting Gbx2 leads to severe disruption of the histogenesis of the thalamus in mice, demonstrating an essential role of Gbx2 in this brain structure. Using inducible genetic fate mapping, we have previously shown that the neuronal precursors for different sets of thalamic nuclei have distinctive onset and duration of Gbx2 expression, suggesting that the dynamic expression of Gbx2 plays an important role in the specification and differentiation of thalamic nuclei. Here, we showed that the Gbx2 lineage exclusively gives rise to neurons but not glia in the thalamus. We performed conditional deletion to examine the temporal requirements of Gbx2 in the developing thalamus in mice. Corresponding to the dynamic and differential expression of Gbx2 in various thalamic nucleus groups, deleting Gbx2 at different embryonic stages disrupts formation of distinct sets of thalamic nuclei. Interestingly, different thalamic nuclei have remarkably different requirements of Gbx2 for the survival of thalamic neurons. Furthermore, although Gbx2 expression persists in many thalamic nuclei until adulthood, only the initial expression of Gbx2 following neurogenesis is crucial for the differentiation of thalamic nuclei. Our results indicate that the dynamic expression of Gbx2 may act as an important determinant in coupling with other developmental programs to generate distinct thalamic nuclei.
Highlights
The mammalian thalamus is composed of dozens of nuclei formed by aggregates of neurons, and each nucleus displays unique cytoarchitecture and connectivity [1]
Gbx2-expressing cells exclusively give rise to thalamic neurons We have previously shown that Gbx2 is mainly expressed in postmitotic cells in the thalamus [6]
We examined the expression of activated caspase 3 (Casp3), which marks cells undergoing apoptosis, in the thalamus following inactivation of at different embryonic stages
Summary
The mammalian thalamus is composed of dozens of nuclei formed by aggregates of neurons, and each nucleus displays unique cytoarchitecture and connectivity [1]. The principal nuclei, which project topographically to specific areas of the cortex, have a primary role in processing and relaying periphery sensory input to the cortex, while other nuclei project broadly to the cortex and regulate the state of consciousness [1,2]. All thalamic neurons are born between embryonic day (E) 10.5 and E16.5 in mice [3]. Between E14.5 and E18.5, the thalamus is gradually partitioned into discrete neuronal groups, signifying the differentiation of thalamic nuclei [1]. The individual thalamic nucleus becomes recognizable after birth in mice [1]. Little is known about the molecular and cellular mechanisms that govern the specification, differentiation, and selective aggregation of thalamic neurons to form distinct nuclei
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