The Prethalamus Is Established during Gastrulation and Influences Diencephalic Regionalization

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Abstract
The vertebrate neural plate contains distinct domains of gene expression, prefiguring the future brain areas. In this study, we draw an extended expression map of the rostral neural plate that reveals discrete domains inside the presumptive posterior forebrain. We show, by fate mapping, that these well-defined cell populations will develop into specific diencephalic regions. To address whether these early subterritories are already committed to restricted identities, we began to analyse the consequences of ablation and transplantation of these specific cell populations. We found that precursors of the prethalamus are already specified and irreplaceable at late gastrula stage, because ablation of these cells results in loss of prethalamic markers. Moreover, when transplanted into the ectopic environment of the presumptive hindbrain, these cells still pursue their prethalamic differentiation program. Finally, transplantation of these precursors, in the rostral-most neural epithelium, induces changes in cell identity in the surrounding host forebrain. This cell–non-autonomous property led us to propose that these committed prethalamic precursors may play an instructive role in the regionalization of the developing diencephalon. During the earliest stages of development, the brain is first formed as a simple sheet of cells called the neural plate. Although the plate looks homogenous, it contains distinct domains that can be identified by differential gene expression. These domains correspond to distinct future brain areas. In this study, we examined gene expression patterns in an area of the neural plate that later forms the forebrain to show that well-defined cell populations will develop into specific forebrain regions, such as the prethalamus, thalamus, hypothalamus, and epithalamus. We then tested whether these early neural plate subterritories are fully committed to a particular forebrain identity. We found that precursors of the prethalamus are not replaceable by other neighbouring cells, because ablation of these cells results in loss of prethalamus development. Moreover, when prethalamus precursors were moved into the environment of the presumptive hindbrain, the cells still pursued their prethalamic differentiation program. Finally, when the prethalamic precursors were moved to areas of the future forebrain, they transformed the surrounding host forebrain. We propose that the committed prethalamic precursors play an instructive role in the regionalization of the developing forebrain.