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Mid-hindbrain Development: New Insights, New Disorders…

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The brain area commonly referred to as mid-hindbrain region comprises the midbrain and the most anterior part of the hindbrain, the so-called rhombomere 1. This brain region is defined by its developmental origin, since a central structure for the development of both regions is the boundary between them, the ...

The brain area commonly referred to as mid-hindbrain region comprises the midbrain and the most anterior part of the hindbrain, the so-called rhombomere 1. This brain region is defined by its developmental origin, since a central structure for the development of both regions is the boundary between them, the mid-hindbrain boundary (MHB) also called the isthmic organiser (IsO) or the mid-hindbrain organiser (MHO). The terms IsO or MHO allude to an organiser region the MHB incorporates, which is essential for growth and patterning of the midbrain and anterior hindbrain. Dorsal midbrain and dorsal anterior hindbrain develop into tectum and cerebellum, respectively; while the ventral part gives rise to glutamatergic, GABAergic, cholinergic, dopaminergic, and serotonergic neurons that assemble into different nuclei, including the red nucleus, the substantia nigra pars reticularis, the oculomotor complex, the trochlear nucleus, the ventral tegmental area, the substantia nigra pars compacta, and the serotonergic dorsal Raphe nuclei.

Malformations or dysfunctions of these mid-hindbrain derived neurons are associated with many human brain disorders. Many of those disorders are based on neurodevelopmental malformations, like ataxias, sensory-motor gating deficits and psychiatric disorders, the later including bipolar mood disorders, schizophrenia and addiction. The recent progress in neuroimaging and genetic technologies provided a deep insight into a wide spectrum of congenital disorder of mid- and hindbrain, which are largely caused by neurodevelopmental malformations. Thus, there is a renewed interest in understanding the mechanisms that regulate the development of these brain regions. Despite great advances in understanding normal and abnormal development of the mid-hindbrain area in mouse, chick and zebrafish, many unresolved issues remain that cloud our view of the assembly of these brain structures.

More knowledge about the mechanisms underlying the assembly of the mid-hindbrain will not only provide insights into basic patterning processes in brain development, but also help clinical understanding of neural disorders associated with these brain regions and potentially facilitate therapies for those disorders.

The Research Topic aims to highlight and cover the current understanding of the patterning of those regions in different animal models. Contributors are welcome to submit reviews, mini-reviews, commentaries, perspectives and original research articles.


Keywords: midbrain, mid-hindbrain boundary, cerebellum, neural development


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