Regulating the dorsal neural tube expression of Ptf1a through a distal 3′ enhancer
| Autor: | John M. Avila, Jane E. Johnson, David Meredith, Rahul K. Kollipara, Bishakha Mona |
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| Rok vydání: | 2016 |
| Předmět: |
Transcriptional Activation
0301 basic medicine Nervous system Neural Tube PAX6 Transcription Factor Mice Transgenic Chick Embryo Regulatory Sequences Nucleic Acid Biology Retina Article Conserved sequence Mice 03 medical and health sciences 0302 clinical medicine Cerebellum medicine Animals Enhancer Molecular Biology Transcription factor Zinc finger Genetics Base Sequence SOXB1 Transcription Factors Stem Cells Neural tube Gene Expression Regulation Developmental Cell Differentiation Zinc Fingers Cell Biology Cell biology Electroporation 030104 developmental biology medicine.anatomical_structure Spinal Cord GDF7 PAX6 030217 neurology & neurosurgery Transcription Factors Developmental Biology |
| Zdroj: | Developmental Biology. 418:216-225 |
| ISSN: | 0012-1606 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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