Fgf15 regulates thalamic development by controlling the expression of proneural genes.

The establishment of the brain structural complexity requires a precisely orchestrated interplay between extrinsic and intrinsic signals modulating cellular mechanisms to guide neuronal differentiation. However, little is known about the nature of these signals in the diencephalon, a complex brain region that processes and relays sensory and motor information to and from the cerebral cortex and subcortical structures. Morphogenetic signals from brain organizers regulate histogenetic processes such as cellular proliferation, migration, and differentiation.

FGF8 activates proliferation and migration in mouse post-natal oligodendrocyte progenitor cells.

Fibroblast growth factor 8 (FGF8) is a key molecular signal that is necessary for early embryonic development of the central nervous system, quickly disappearing past this point. It is known to be one of the primary morphogenetic signals required for cell fate and survival processes in structures such as the cerebellum, telencephalic and isthmic organizers, while its absence causes severe abnormalities in the nervous system and the embryo usually dies in early stages of development. In this work, we have observed a new possible therapeutic role for this factor in demyelinating disorders, such as leukodystrophy or multiple sclerosis.

A high-resolution spatiotemporal atlas of gene expression of the developing mouse brain.

To provide a temporal framework for the genoarchitecture of brain development, we generated in situ hybridization data for embryonic and postnatal mouse brain at seven developmental stages for ∼2,100 genes, which were processed with an automated informatics pipeline and manually annotated. This resource comprises 434,946 images, seven reference atlases, an ontogenetic ontology, and tools to explore coexpression of genes across neurodevelopment. Gene sets coinciding with developmental phenomena were identified.

Wnt signal specifies the intrathalamic limit and its organizer properties by regulating Shh induction in the alar plate.

The structural complexity of the brain depends on precise molecular and cellular regulatory mechanisms orchestrated by regional morphogenetic organizers. The thalamic organizer is the zona limitans intrathalamica (ZLI), a transverse linear neuroepithelial domain in the alar plate of the diencephalon. Because of its production of Sonic hedgehog, ZLI acts as a morphogenetic signaling center.

Molecular regionalization of the diencephalon.

The anatomic complexity of the diencephalon depends on precise molecular and cellular regulative mechanisms orchestrated by regional morphogenetic organizers at the neural tube stage. In the diencephalon, like in other neural tube regions, dorsal and ventral signals codify positional information to specify ventro-dorsal regionalization. Retinoic acid, Fgf8, BMPs, and Wnts signals are the molecular factors acting upon the diencephalic epithelium to specify dorsal structures, while Shh is the main ventralizing signal.

The development of the thalamic motor learning area is regulated by Fgf8 expression.

Habenular nuclei play a key role in the control of motor and cognitive behavior, processing emotion, motivation, and reward values in the brain. Thus, analysis of the molecular and cellular mechanisms underlying the development and evolution of this region will contribute to a better understanding of brain function. The Fgf8 gene is expressed in the dorsal midline of the diencephalon, close to the area in which the habenular region will develop.