Abstract
The auditory system contains a diverse array of interconnected anatomical structures that mediate the perception of sound. The cochlear nucleus of the hindbrain serves as the initial site of convergence for auditory stimuli, while the inferior colliculus of the midbrain serves as an integration and relay station for all ascending auditory information. We used Genetic Inducible Fate Mapping (GIFM) to determine how the timing of Wnt1 expression is related to the competency states of auditory neuron progenitors. We demonstrate that the Wnt1 lineage defines progenitor pools of auditory neurons in the developing midbrain and hindbrain. The timing of Wnt1 expression specifies unique cell types during embryogenesis and follows a mixed model encompassing a brief epoch of de novo expression followed by rapid and progressive lineage restriction to shape the inferior colliculus. In contrast, Wnt1 fate mapping of the embryonic hindbrain revealed de novo induction of Wnt1 in auditory hindbrain progenitors, which is related to the development of biochemically distinct neurons in the cochlear nucleus. Thus, we uncovered two modes of lineage allocation that explain the relationship between the timing of Wnt1 expression and the development of the cochlear nucleus and the inferior colliculus. Finally, our analysis of Wnt1sw/sw mutant mice demonstrated a functional requirement of Wnt1 for the development of auditory midbrain and hindbrain neurons. Collectively, our study provides a deeper understanding of Wnt1 lineage allocation and function in mammalian brain development.
Highlights
The central auditory system is comprised of several anatomically distinct brain regions that are essential for normal sound processing
Expression of Wnt1 was observed in the lower rhombic lip (LRL) at E12.5 (Figures 1J,L) and consisted of early projections (Figure 1L, arrows), which contributed to the broadened expression domain, as well as cells emanating from the LRL
We took advantage of Genetic Inducible Fate Mapping (GIFM) to assess two distinct models of how Wnt1-expressing progenitors contribute to biochemically distinct neurons of the auditory hindbrain and midbrain
Summary
The central auditory system is comprised of several anatomically distinct brain regions that are essential for normal sound processing. The innervation and organization of the auditory hindbrain and midbrain are largely established before the onset of hearing (Friauf and Kandler, 1990; Kandler and Friauf, 1993; Gurung and Fritzsch, 2004) These findings suggest that developmental, but perhaps not activity-dependent, mechanisms play a primary role in the functional organization of the auditory system. Concurrent with establishing mature neuronal phenotypes within the cochlear nucleus is the differential expression of the calcium-binding proteins parvalbumin (PV), calretinin (CALR), and calbindin (CALB) (Fredrich et al, 2009). It is unresolved how biochemically diverse neurons in the mature auditory system are established during development
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