Positive autofeedback regulation of Ptf1a transcription generates the levels of PTF1A required to generate itch circuit neurons

Bishakha Mona, Juan Villarreal, Trisha K. Savage, Rahul K. Kollipara, Brooke E. Boisvert, Jane E. Johnson

Research output: Contribution to journalArticle

Abstract

Peripheral somatosensory input is modulated in the dorsal spinal cord by a network of excitatory and inhibitory interneurons. PTF1A is a transcription factor essential in dorsal neural tube progenitors for specification of these inhibitory neurons. Thus, mechanisms regulating Ptf1a expression are key for generating neuronal circuits underlying somatosensory behaviors. Mutations targeted to distinct cis-regulatory elements for Ptf1a in mice, tested the in vivo contribution of each element individually and in combination. Mutations in an autoregulatory enhancer resulted in reduced levels of PTF1A, and reduced numbers of specific dorsal spinal cord inhibitory neurons, particularly those expressing Pdyn and Gal. Although these mutants survive postnatally, at ∼3-5 wk they elicit a severe scratching phenotype. Behaviorally, the mutants have increased sensitivity to itch, but acute sensitivity to other sensory stimuli such as mechanical or thermal pain is unaffected. We demonstrate a requirement for positive transcriptional autoregulatory feedback to attain the level of the neuronal specification factor PTF1A necessary for generating correctly balanced neuronal circuits.

Original languageEnglish (US)
Pages (from-to)621-636
Number of pages16
JournalGenes and Development
Volume34
Issue number9-10
DOIs
StatePublished - May 1 2020

Keywords

  • Autoregulation
  • BHLH transcription factor
  • Cell fate specification
  • Inhibitory neuron
  • Itch
  • Neuronal identity
  • Somatosensory
  • Spinal cord development
  • Transcriptional control

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Fingerprint Dive into the research topics of 'Positive autofeedback regulation of Ptf1a transcription generates the levels of PTF1A required to generate itch circuit neurons'. Together they form a unique fingerprint.

  • Cite this