Genetic mapping of Foxb1‐cell lineage shows migration from caudal diencephalon to telencephalon and lateral hypothalamus

Abstract

The hypothalamus is a brain region with vital functions, and alterations in its development can cause human disease. However, we still do not have a complete description of how this complex structure is put together during embryonic and early postnatal stages. Radially oriented, outside-in migration of cells is prevalent in the developing hypothalamus. In spite of this, cell contingents from outside the hypothalamus as well as tangential hypothalamic migrations also have an important role. Here we study migrations in the hypothalamic primordium by genetically labeling the Foxb1 diencephalic lineage. Foxb1 is a transcription factor gene expressed in the neuroepithelium of the developing neural tube with a rostral expression boundary between caudal and rostral diencephalon, and therefore appropriate for marking migrations from caudal levels into the hypothalamus. We have found a large, longitudinally oriented migration stream apparently originating in the thalamic region and following an axonal bundle to end in the anterior portion of the lateral hypothalamic area. Additionally, we have mapped a specific expansion of the neuroepithelium into the rostral diencephalon. The expanded neuroepithelium generates abundant neurons for the medial hypothalamus at the tuberal level. Finally, we have uncovered novel diencephalon-to-telencephalon migrations into septum, piriform cortex and amygdala.

Reduction in 50-kHz call-numbers and suppression of tickling-associated positive affective behaviour after lesioning of the lateral hypothalamic parvafox nucleus in rats

“…One limitation of the present study was that there was no possibility to assess the effect of the excitotoxin lesion on the Foxb1 sub-population. Using a strain of mice that expresses Cre recombinase under the control of the Foxb1-promoter [68], it has been possible to characterise in detail the topography and the morphological features of the Foxb1-expressing cells in the parvafox nucleus [4]. To date, all attempts to map Foxb1-immunoreactivity in wild-type mice or rats using specific antibodies have failed.…”

Birthdate of parvalbumin-neurons in the Parvafox-nucleus of the lateral hypothalamus

“…The Foxb1 pattern of expression evolves with time with widespread expression in early stages of development and very restricted one in the adult. Therefore, it is possible to make a distinction between E9/E10, (Alvarez-Bolado et al, 2000), when Foxb1 expressing neurons are born (Zhao et al, 2008) and are confined to the posterior hypothalamus and E13/14 when Foxb1-expressing cells leave the mammillary region and migrate in rostral direction. They reach the tuberal region of the lateral hypothalamus, giving rise to the Foxb1-expressing neurons belonging to the Parvafox-nucleus observed postnatally (Bilella et al, 2014).…”

Role of NeuroepithelialSonic hedgehogin Hypothalamic Patterning

“…In this conditional allele, exon 2 of Shh is flanked by loxP sites (Dassule et al, 2000;Lewis et al, 2001). Exon 2 encodes approximately one-half of the active N-terminal Shh signal, essential for Shh function (Mann and Beachy, 2004 In Shh-c mutants, exon 2 of the Shh locus has been deleted in the entire Foxb1 lineage, including the caudal diencephalon, the posterior ventral hypothalamus, and the diencephalic ventral midline (Zhao et al, 2007(Zhao et al, , 2008. In Shh-c mutants, whenever transcription from the Shh locus occurs (in cells of the Foxb1 lineage), the recombined Shh locus produces a truncated, nonfunctional mRNA lacking exon 2.…”

“…This line expresses Cre recombinase in the mouse diencephalon (Zhao et al, 2007(Zhao et al, , 2008, and it is a knock-in-knock-out generating Foxb1 heterozygous animals. These heterozygotes do not show haploinsufficiency and can be considered identical with wild type (WT) (Dou et Foxb1-Cre/ROSA26R lineage reporter line.…”

“…Since diencephalic Foxb1 expression is mostly transient (Zhao et al, 2007(Zhao et al, , 2008, we used a lineage reporter mouse line to identify the regions in which a phenotype can be expected. In these embryos, cells that have expressed Foxb1, as well as cells derived from them, express ␤-galactosidase permanently, allowing for the identification of the regions in which Foxb1-driven Cre recombination has taken place (see Materials and Methods).…”