A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea

Meenakshi Prajapati-DiNubila, Ana Benito-Gonzalez, Erin Jennifer Golden, Shuran Zhang, Angelika Doetzlhofer

Research output: Contribution to journalArticle

Abstract

The mammalian auditory sensory epithelium has one of the most stereotyped cellular patterns known in vertebrates. Mechano-sensory hair cells are arranged in precise rows, with one row of inner and three rows of outer hair cells spanning the length of the spiral-shaped sensory epithelium. Aiding such precise cellular patterning, differentiation of the auditory sensory epithelium is precisely timed and follows a steep longitudinal gradient. The molecular signals that promote auditory sensory differentiation and instruct its graded pattern are largely unknown. Here, we identify Activin A and its antagonist follistatin as key regulators of hair cell differentiation and show, using mouse genetic approaches, that a local gradient of Activin A signaling within the auditory sensory epithelium times the longitudinal gradient of hair cell differentiation. Furthermore, we provide evidence that Activin-type signaling regulates a radial gradient of terminal mitosis within the auditory sensory epithelium, which constitutes a novel mechanism for limiting the number of inner hair cells being produced.

Original languageEnglish (US)
JournaleLife
Volume8
DOIs
StatePublished - Jun 12 2019

Fingerprint

Follistatin
Cochlea
Cell Differentiation
Epithelium
Cells
Outer Auditory Hair Cells
Inner Auditory Hair Cells
Activins
Mitosis
Vertebrates
activin A

Keywords

  • activin signaling
  • auditory cell differentiation
  • cochlea
  • developmental biology
  • follistatin
  • hair cell
  • inner ear
  • mouse
  • neuroscience

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea. / Prajapati-DiNubila, Meenakshi; Benito-Gonzalez, Ana; Golden, Erin Jennifer; Zhang, Shuran; Doetzlhofer, Angelika.

In: eLife, Vol. 8, 12.06.2019.

Research output: Contribution to journalArticle

Prajapati-DiNubila, Meenakshi ; Benito-Gonzalez, Ana ; Golden, Erin Jennifer ; Zhang, Shuran ; Doetzlhofer, Angelika. / A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea. In: eLife. 2019 ; Vol. 8.
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