The Role of Atonal Factors in Mechanosensory Cell Specification and Function

Mol Neurobiol. 2015 Dec;52(3):1315-1329. doi: 10.1007/s12035-014-8925-0. Epub 2014 Oct 23.

Abstract

Atonal genes are basic helix-loop-helix transcription factors that were first identified as regulating the formation of mechanoreceptors and photoreceptors in Drosophila. Isolation of vertebrate homologs of atonal genes has shown these transcription factors to play diverse roles in the development of neurons and their progenitors, gut epithelial cells, and mechanosensory cells in the inner ear and skin. In this article, we review the molecular function and regulation of atonal genes and their targets, with particular emphasis on the function of Atoh1 in the development, survival, and function of hair cells of the inner ear. We discuss cell-extrinsic signals that induce Atoh1 expression and the transcriptional networks that regulate its expression during development. Finally, we discuss recent work showing how identification of Atoh1 target genes in the cerebellum, spinal cord, and gut can be used to propose candidate Atoh1 targets in tissues such as the inner ear where cell numbers and biochemical material are limiting.

Keywords: Atoh1; Atonal; Cochlea; Hair cells; Sensory; Transcription factors; bHLH.

MeSH terms

  • Amino Acid Sequence
  • Animal Structures / physiology
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / classification
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Compound Eye, Arthropod / cytology
  • Compound Eye, Arthropod / embryology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology
  • Evolution, Molecular
  • Gene Expression Regulation, Developmental / physiology*
  • Hair Cells, Auditory / physiology
  • Humans
  • Intestines / cytology
  • Intestines / embryology
  • Intestines / growth & development
  • Invertebrates / physiology
  • Mechanoreceptors / physiology*
  • Mechanotransduction, Cellular / physiology*
  • Merkel Cells / metabolism
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neurogenesis / physiology
  • Photoreceptor Cells, Invertebrate / physiology
  • Phylogeny
  • Sense Organs / physiology
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction / physiology
  • Transcription, Genetic
  • Vertebrates / physiology

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Drosophila Proteins
  • Nerve Tissue Proteins
  • ato protein, Drosophila