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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Morphogenesis and Patterning
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1537505

Lmx1a is essential for marginal cell differentiation and stria vascularis formation

Provisionally accepted
Justine Marie Renauld Justine Marie Renauld 1Igor Iskusnykh Igor Iskusnykh 2Ebenezer N Yamoah Ebenezer N Yamoah 3Richard J Smith Richard J Smith 4Corentin Affortit Corentin Affortit 4David Z He David Z He 1Huizhan Li Huizhan Li 1David Nichols David Nichols 1Judith Bouma Judith Bouma 1Mahesh Nayak Mahesh Nayak 1Xin Weng Xin Weng 5Tianli Qin Tianli Qin 5Mai Har Sham Mai Har Sham 5Victor Chizhikov Victor Chizhikov 2*Bernd Fritzsch Bernd Fritzsch 6*
  • 1 Creighton University, Omaha, Nebraska, United States
  • 2 University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee, United States
  • 3 University of Arizona, College of Medicine, Pheonix, United States
  • 4 The University of Iowa, Iowa City, Iowa, United States
  • 5 The Chinese University of Hong Kong, Shatin, Hong Kong Region, China
  • 6 University of Nebraska Medical Center, Omaha, United States

The final, formatted version of the article will be published soon.

    The transcription factor Lmx1a is widely expressed during early inner ear development, and mice lacking Lmx1a expression showed fusion of cochlear and vestibular hair cells and lack the formation of the ductus reuniens and the endolymphatic sac. Lmx1a dreher (Lmx1a dr/dr ), a recessive null mutation, showed non-functional Lmx1a expression expanded from the outer sulcus to the stria vascularis and Reissner's membrane. In the absence of Lmx1a, we observe an absence of proteins specific to the stria vascularis, such as BSND and KCNQ1 for marginal cells and CD44 for intermediate cells. Further analysis of the superficial cell layer epithelium at the expected stria vascularis location showed that the future intermediate cells migrated during embryonic development but then disappeared, due to the lack of signaling factors for marginal cell survival. Using antibodies against Pendrin (Slc26a4) in the Lmx1a knockout (KO) mice, we observe an expansion of Pendrin expression across the stria vascularis and Reissner's membrane. Moreover, without Lmx1a expression, no endocochlear potential is observed. The finding highlights the critical role of Lmx1a in inner ear development, particularly in the differentiation of cochlear and vestibular structures, the recruitment of pigment cells, and the expression of proteins essential for hearing and balance.

    Keywords: lmx1a, Pendrin, SLC26A4, Stria Vascularis, spiral prominence, Pigment cells

    Received: 04 Dec 2024; Accepted: 03 Feb 2025.

    Copyright: © 2025 Renauld, Iskusnykh, Yamoah, Smith, Affortit, He, Li, Nichols, Bouma, Nayak, Weng, Qin, Sham, Chizhikov and Fritzsch. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Victor Chizhikov, University of Tennessee Health Science Center (UTHSC), Memphis, 38163-0002, Tennessee, United States
    Bernd Fritzsch, University of Nebraska Medical Center, Omaha, United States

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