Abstract
The epithalamus, which is dorsal to the thalamus, consists of the habenula, pineal gland and third ventricle choroid plexus and plays important roles in the stress response and sleep–wake cycle in vertebrates. During development, the epithalamus arises from the most dorsal part of prosomere 2. However, the mechanism underlying epithalamic development remains largely unknown. Foxg1 is critical for the development of the telencephalon, but its role in diencephalic development has been under-investigated. Patients suffering from FOXG1-related disorders exhibit severe anxiety, sleep disturbance and choroid plexus cysts, indicating that Foxg1 likely plays a role in epithalamic development. In this study, we identified the specific expression of Foxg1 in the developing epithalamus. Using a “self-deletion” approach, we found that the habenula significantly expanded and included an increased number of habenular subtype neurons. The innervations, particularly the habenular commissure, were severely impaired. Meanwhile, the Foxg1 mutants exhibited a reduced pineal gland and more branched choroid plexus. After ablation of Foxg1 no obvious changes in Shh and Fgf signalling were observed, suggesting that Foxg1 regulates the development of the epithalamus without the involvement of Shh and Fgfs. Our findings provide new insights into the regulation of the development of the epithalamus.
Highlights
The epithalamus, which consists of the habenula, pineal gland, and third ventricle choroid plexus (3rdChp), is involved in many functions, including motor control, the sleep–wake cycle and stress responses [1,2,3]
Foxg1 is expressed in the developing dorsal diencephalon, and ablation of Foxg1 leads to an impaired epithalamus The forkhead box transcription factor Foxg1 has been reported to be critical for telencephalic development [17]
Considering the symptoms, including poor sleep patterns, emotional disorders and choroid plexus cysts, observed in patients suffering from FOXG1 syndrome [21,22,23], we suspect that Foxg1 plays an important role in the developing diencephalon
Summary
The epithalamus, which consists of the habenula, pineal gland, and third ventricle choroid plexus (3rdChp), is involved in many functions, including motor control, the sleep–wake cycle and stress responses [1,2,3]. The pineal gland is critical for the regulation of circadian rhythms due to its production of melatonin [6], and the choroid plexus synthesizes cerebrospinal fluid (CSF) and many growth factors, including fibroblasts and insulin-like and platelet-derived growth factors, and plays important roles, such as providing a route for nutrients and removing by-products of metabolism [7, 8]. In the presumptive epithalamic progenitor domain, the most anterior area containing the roof plate develops into the 3rdChp, while the adjacent part generates the habenular commissure, paired habenulas and pineal gland. The molecular and cellular mechanisms underlying the development of the epithalamus still remain largely unknown
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