Regulating the dorsal neural tube expression of Ptf1a through a distal 3′ enhancer

Bishakha Mona, John M. Avila, David M. Meredith, Rahul K. Kollipara, Jane E. Johnson

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Generating the correct balance of inhibitory and excitatory neurons in a neural network is essential for normal functioning of a nervous system. The neural network in the dorsal spinal cord functions in somatosensation where it modulates and relays sensory information from the periphery. PTF1A is a key transcriptional regulator present in a specific subset of neural progenitor cells in the dorsal spinal cord, cerebellum and retina that functions to specify an inhibitory neuronal fate while suppressing excitatory neuronal fates. Thus, the regulation of Ptf1a expression is critical for determining mechanisms controlling neuronal diversity in these regions of the nervous system. Here we identify a sequence conserved, tissue-specific enhancer located 10.8 kb 3′ of the Ptf1a coding region that is sufficient to direct expression to dorsal neural tube progenitors that give rise to neurons in the dorsal spinal cord in chick and mouse. DNA binding motifs for Paired homeodomain (Pd-HD) and zinc finger (ZF) transcription factors are required for enhancer activity. Mutations in these sequences implicate the Pd-HD motif for activator function and the ZF motif for repressor function. Although no repressor transcription factor was identified, both PAX6 and SOX3 can increase enhancer activity in reporter assays. Thus, Ptf1a is regulated by active and repressive inputs integrated through multiple sequence elements within a highly conserved sequence downstream of the Ptf1a gene.

Original languageEnglish (US)
Pages (from-to)216-225
Number of pages10
JournalDevelopmental Biology
Volume418
Issue number1
DOIs
StatePublished - Oct 1 2016

Keywords

  • Dorsal spinal cord
  • Inhibitory neurons
  • Neuronal specification
  • PTF1A
  • Tissue-specific enhancer
  • Transcriptional regulation

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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