AUTHOR=Brown Stephen , Zervas Mark 

TITLE=Temporal Expression of Wnt1 Defines the Competency State and Terminal Identity of Progenitors in the Developing Cochlear Nucleus and Inferior Colliculus

JOURNAL=Frontiers in Neuroanatomy

VOLUME=11

YEAR=2017

URL=https://www.frontiersin.org/journals/neuroanatomy/articles/10.3389/fnana.2017.00067

DOI=10.3389/fnana.2017.00067

ISSN=1662-5129

ABSTRACT=<p>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 <underline>G</underline>enetic <underline>I</underline>nducible <underline>F</underline>ate <underline>M</underline>apping (GIFM) to determine how the timing of <italic>Wnt1</italic> expression is related to the competency states of auditory neuron progenitors. We demonstrate that the <italic>Wnt1</italic> lineage defines progenitor pools of auditory neurons in the developing midbrain and hindbrain. The timing of <italic>Wnt1</italic> expression specifies unique cell types during embryogenesis and follows a mixed model encompassing a brief epoch of <italic>de novo</italic> expression followed by rapid and progressive lineage restriction to shape the inferior colliculus. In contrast, <italic>Wnt1</italic> fate mapping of the embryonic hindbrain revealed <italic>de novo</italic> induction of <italic>Wnt1</italic> 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 <italic>Wnt1</italic> expression and the development of the cochlear nucleus and the inferior colliculus. Finally, our analysis of <italic>Wnt1<sup>sw/sw</sup></italic> mutant mice demonstrated a functional requirement of <italic>Wnt1</italic> for the development of auditory midbrain and hindbrain neurons. Collectively, our study provides a deeper understanding of <italic>Wnt1</italic> lineage allocation and function in mammalian brain development.</p>