The bHLH transcription factor Olig3 marks the dorsal neuroepithelium of the hindbrain and is essential for the development of brainstem nuclei

Abstract

The Olig3 gene encodes a bHLH factor that is expressed in the ventricular zone of the dorsal alar plate of the hindbrain. We found that the Olig3 + progenitor domain encompassed subdomains that co-expressed Math1, Ngn1, Mash1 and Ptf1a. Olig3 + cells give rise to neuronal types in the dorsal alar plate that we denote as class A neurons. We used genetic lineage tracing to demonstrate that class A neurons contribute to the nucleus of the solitary tract and to precerebellar nuclei. The fate of class A neurons was not correctly determined in Olig3 mutant mice. As a consequence, the nucleus of the solitary tract did not form, and precerebellar nuclei, such as the inferior olivary nucleus, were absent or small. At the expense of class A neurons, ectopic Lbx1 + neurons appeared in the alar plate in Olig3 mutant mice. By contrast, electroporation of an Olig3 expression vector in the chick hindbrain suppressed the emergence of Lbx1 + neurons. Climbing fiber neurons of the inferior olivary nucleus express Foxd3 and require Olig3 as well as Ptf1a for the determination of their fate. We observed that electroporation of Olig3 and Ptf1a expression vectors, but not either alone, induced Foxd3. We therefore propose that Olig3 can cooperate with Ptf1a to determine the fate of climbing fiber neurons of the inferior olivary nucleus.

Homeoprotein Phox2b commands a somatic-to-visceral switch in cranial sensory pathways

“…S4A′). We examined the status of Pou4f1/Brn3a, and its paralogue Pou4f2/Brn3b, broadly expressed in dorsal interneurons of the hindbrain and spinal cord (12,24) (Fig. S5).…”

“…In the hindbrain, relay sensory neurons of the nTS are born from E9.5 to E13.5 (10) in the domain of dA3 progenitors, which extends from rhombomere (r) 4 to r7 (11,12) and switch on Phox2b postmitotically (9). In homozygous Phox2b null embryos, nTS precursors switch on Lmx1b and Rnx/Tlx3 and start migrating ventrally (9)-as they do in heterozygous or wild-type embryos (9,12).…”

“…In homozygous Phox2b null embryos, nTS precursors switch on Lmx1b and Rnx/Tlx3 and start migrating ventrally (9)-as they do in heterozygous or wild-type embryos (9,12). However, at E12.5, most become undetectable using LacZ as a reporter (9).…”

Loss ofPtf1aLeads to a Widespread Cell-Fate Misspecification in the Brainstem, Affecting the Development of Somatosensory and Viscerosensory Nuclei

“…1A-D;Sieber et al, 2007). Some of these populations, such as dA4 and dB1, extend through rh2-7, while others, such as dA3, are present only in some rhombomeres (Sieber et al, 2007;Storm et al, 2009). In contrast to rh2-6, where dA/dB neurons arise throughout neurogenesis, in rh7, dBLa and dBLb neurons arise in a salt-and-pepper pattern from the dorsal VZ after E12 ( Fig.…”

“…1E; Sieber et al, 2007). Fate-mapping and gene expression studies identified dA3 cells as differentiating Lmx1b ϩ /Phox2b ϩ neurons of the nTS, dA4 cells of the caudal brainstem as newborn ION neurons, and dBLb cells as Lmx1b ϩ SpV neurons (Sieber et al, 2007;Storm et al, 2009;D'Autréaux et al, 2011), while the eventual fates of most other dA/dB populations, as well as dBLa cells, remain unknown.…”