The zinc-finger transcription factor GLI3 is a regulator of precerebellar neuronal migration

Abstract

Hindbrain precerebellar neurons arise from progenitor pools at the dorsal edge of the embryonic hindbrain: the caudal rhombic lip. These neurons follow distinct migratory routes to establish nuclei that provide climbing or mossy fiber inputs to the cerebellum. Gli3, a zinc-finger transcription factor in the Sonic hedgehog signaling pathway, is an important regulator of dorsal brain development. We demonstrate that in Gli3-null mutant mice, disrupted neuronal migratory streams lead to a disorganization of precerebellar nuclei. Precerebellar progenitors are properly established in Gli3-null embryos and, using conditional gene inactivation, we provide evidence that Gli3 does not play a cell-autonomous role in migrating precerebellar neurons. Thus, GLI3 likely regulates the development of other hindbrain structures, such as non-precerebellar nuclei or cranial ganglia and their respective projections, which may in turn influence precerebellar migration. Although the organization of non-precerebellar hindbrain nuclei appears to be largely unaffected in absence of Gli3, trigeminal ganglia and their central descending tracts are disrupted. We show that rostrally migrating precerebellar neurons are normally in close contact with these tracts, but are detached in Gli3-null embryos.

Expression levels of sonic hedgehog pathway genes and their targets are upregulated in early clear cell renal cell carcinoma

“…Sonic hedgehog (SHH) signaling is involved in the human embryogenesis of epithelial tissue ( 38 ) and the respiratory system ( 39 ), and it is critical in the development of the nervous system ( 40 - 42 ) and limbs ( 43 , 44 ). Although some authors have suggested that this molecular cascade also remains active in postnatal life in organs such as the brain ( 45 ) or lungs ( 46 ), the signaling becomes silenced in almost all other tissues ( 47 ).…”

Loss of BAF Complex in Developing Cortex Perturbs Radial Neuronal Migration in a WNT Signaling-Dependent Manner

“…With reference to our previous report that BAF complex regulates cortical neurogenesis via suppression of WNT signaling in the developing mouse cortex ( Nguyen et al, 2018 ), we asked whether the neuronal migration phenotype in the BAF complex mutant brain is dependent on WNT signaling. Interestingly, several signaling pathways, including WNT signaling, have been implicated in neuronal migration regulation during brain development ( Siegenthaler and Miller, 2004 ; Hashimoto-Torii et al, 2008 ; Yi et al, 2010 ; Boitard et al, 2015 ; Bocchi et al, 2017 ; Martinez-Chavez et al, 2018 ; Saxena et al, 2018 ). In the case of WNT signaling, it was reported that dynamic regulation of the cascade is necessary for multipolar-to-bipolar morphology transition during radial migration of cortical neurons ( Boitard et al, 2015 ).…”

Single cell atlas of domestic pig brain illuminates the conservation and divergence of cell types at spatial and species levels

“…C18 specifically expressed 19 TF encoding genes (GTF2IRD1, GLI3, ETV1, ID3, SATB1, TEAD1, NPAS4, DACH1, AHR, ARID3B, ONECUT2, KLF5, MEOX1, BNC2, SOX13, TBX18, HIVEP1, and RORA). Among them, GLI3 is required for the maintenaning and fate specifying of cortical progenitors, and it is proposed to regulate the migration of precerebellar neurons [63,64].…”