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Differential vulnerability of cochlear nuclei to Lmx1 deficiency: abnormal patterning and implications for auditory circuitry.

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Τίτλος: Differential vulnerability of cochlear nuclei to Lmx1 deficiency: abnormal patterning and implications for auditory circuitry.
Συγγραφείς: Iskusnykh I; Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Yamoah EN; Department of Translational Sciences, University of Arizona, College of Medicine-Phoenix, AZ 85004, USA., Chizhikov VV; Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Fritzsch B; Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: bfritzsch@unmc.edu.
Πηγή: Neuroscience letters [Neurosci Lett] 2026 Aug; Vol. 883, pp. 138669. Date of Electronic Publication: 2026 Jun 30.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Scientific Publishers Ireland Country of Publication: Ireland NLM ID: 7600130 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7972 (Electronic) Linking ISSN: 03043940 NLM ISO Abbreviation: Neurosci Lett Subsets: MEDLINE
Imprint Name(s): Publication: Limerick : Elsevier Scientific Publishers Ireland
Original Publication: Amsterdam, Elsevier/North-Holland.
Ιατρικοί όροι (MeSH): Cochlear Nucleus*/metabolism , Cochlear Nucleus*/embryology , Cochlear Nucleus*/growth & development , LIM-Homeodomain Proteins*/genetics , LIM-Homeodomain Proteins*/deficiency , LIM-Homeodomain Proteins*/metabolism , Transcription Factors*/genetics , Transcription Factors*/deficiency , Transcription Factors*/metabolism , Auditory Pathways*/metabolism, Animals ; Mice, Knockout ; Mice
Περίληψη: Precise regulation of progenitor identity is essential for the formation of functional auditory circuits. Cochlear nuclei arise from two major progenitor populations: Atoh1-expressing progenitors generate excitatory glutamatergic neurons, while Ptf1a-expressing progenitors generate inhibitory GABAergic and glycinergic neurons. Lmx1a and Lmx1b, expressed in the hindbrain roof plate, maintain Atoh1 expression in lower rhombic lip progenitors that give rise to excitatory neurons of the cochlear nuclei. Detailed analysis using dye tracing of cochlear and vestibular central projections revealed an overall reduction of input in both Lmx1a knockout mice and Lmx1a knockout mice with additonal loss of one copy of Lmx1b, although projections to the dorsal cochlear nucleus (DCN) remain relatively preserved. Dye insertion at the crossing of the acoustic stria demonstrate a progressive loss of the ventral acoustic stria (VAS) and its altered trajectory between the trigeminal and restiform body in Lmx1a-/- and Lmx1a-/-;Lmx1b+/- mice. Together, these data show that the anteroventral cochlear nucleus (AVCN) is most severely affected at both embryonic and postnatal stages, showing loss and reduction of central projections. Ultimately, these findings identify Lmx1-dependent regulatory activity as a critical checkpoint for the proper development and connectivity of auditory pathways.
(Copyright © 2026 Elsevier B.V. All rights reserved.)
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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Grant Information: R01 DC015135 United States DC NIDCD NIH HHS; R01 DC022866 United States DC NIDCD NIH HHS; R01 DC016099 United States DC NIDCD NIH HHS; R01 DC015252 United States DC NIDCD NIH HHS; P01 AG051443 United States AG NIA NIH HHS; R01 NS127973 United States NS NINDS NIH HHS; R01 AG060504 United States AG NIA NIH HHS
Contributed Indexing: Keywords: Central auditory projections; Cochlear nuclei; Inner ear; Lmx1a; Lmx1b; Rhombic lip
Substance Nomenclature: 0 (LIM-Homeodomain Proteins)
0 (Transcription Factors)
0 (Lmx1a protein, mouse)
0 (LIM homeobox transcription factor 1 beta)
Entry Date(s): Date Created: 20260630 Date Completed: 20260806 Latest Revision: 20260910
Update Code: 20260910
PubMed Central ID: PMC13552370
DOI: 10.1016/j.neulet.2026.138669
PMID: 42379263
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1872-7972
DOI:10.1016/j.neulet.2026.138669