The TrkA/NGF receptor is essential for the survival and differentiation of sensory neurons. The molecular mechanisms regulating tissue and stage-specific expression of TrkA are largely unknown. The Brn3a POU-domain transcription factor has been implicated in the development of the PNS and proposed as a transcription regulator for TrkA. The molecular mechanisms underlying the regulation of TrkA by Brn3a is unclear. In this study, we provide genetic,transgenic and biochemical evidence that Brn3a binds to novel, specific sites in the 457 bp enhancer that regulates TrkA expression in embryonic sensory neurons. We employ Bax-knockout mice, in which sensory neurons no longer require neurotrophins for survival, to uncouple TrkA-dependent cell death from downregulation of TrkA expression. In addition, when mutagenized, the novel Brn3a-binding sites identified fail to drive appropriate reporter transgene expression in sensory neurons. Thus, TrkA, a gene that is crucial for the differentiation and survival of sensory nociceptive neurons, requires Brn3a to maintain normal transcriptional activity.
History of our journals
As our publisher, The Company of Biologists, turns 100 years old, read about Development’s journey and highlights from some its first issues, and explore the history of each of our sister journals: Journal of Cell Science, Journal of Experimental Biology, Disease Models & Mechanisms and Biology Open.
Call for papers – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues
Development invites you to submit your latest research to our upcoming special issue – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues. This issue will be coordinated by Guest Editors Meritxell Huch (Max Planck Institute of Molecular Cell Biology and Genetics, Germany) and Mansi Srivastava (Harvard University and Museum of Comparative Zoology, USA), working alongside our team of academic Editors. Submit your articles by 15 May 2025.
A case for broadening our view of mechanism in developmental biology
In this Perspective, B. Duygu Özpolat and colleagues survey researchers on their views on what it takes to infer mechanism in developmental biology. They examine what factors shape our idea of what we mean by ‘mechanism’ and suggest a path forward that embraces a broad outlook on the diversity of studies that advance knowledge in our field.
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