The p75 neurotrophin receptor is required for the survival of neuronal progenitors and normal formation of the basal forebrain, striatum, thalamus and neocortex

• DOI: 10.1242/dev.181933
• Publication Date: 2019-09-05T14:48:46Z
• Authors: Sonja Meier; Fabienne Alfonsi; Nyoman D. Kurniawan; Michael R. Milne; Maria A. Kasherman; Alessio Delogu; Michael Piper; Elizabeth J. Coulson
• Keywords: Neuronal progenitor survival; Golgi Apparatus; 32 Biomedical and Clinical Sciences; Neocortex; Regenerative Medicine; Receptor, Nerve Growth Factor; 1309 Developmental Biology; Nestin; Mice; Neural Stem Cells; Thalamus; Nerve Growth Factor; Pediatric; Neurons; 0303 health sciences; anzsrc-for: 42 Health sciences; Caspase 3; Pyramidal Cells; P75 knockout mouse; Organ Size; Brain development; Thalamic midline fusion; Neurological; anzsrc-for: 3209 Neurosciences; Stem Cell Research - Nonembryonic - Non-Human; Receptor; 570; 571; Basal Forebrain; Cell Survival; 1.1 Normal biological development and functioning; Neurogenesis; 610; 03 medical and health sciences; anzsrc-for: 32 Biomedical and Clinical Sciences; Interneurons; anzsrc-for: 31 Biological sciences; 1312 Molecular Biology; Animals; Molecular Biology; Cell Proliferation; Cortical development; P75 neurotrophin receptor; Neurosciences; Stem Cell Research; Newborn; Neostriatum; anzsrc-for: 11 Medical and Health Sciences; Animals, Newborn; 3209 Neurosciences; anzsrc-for: 06 Biological Sciences; Developmental Biology

During development, the p75 neurotrophin receptor (p75NTR) is widely expressed in the nervous system where it regulates neuronal differentiation, migration and axonal outgrowth. p75NTR also mediates the survival and death of newly born neurons, with functional outcomes being dependent on both timing and cellular context. Here we show that knockout of p75NTR from embryonic day 10 (E10) in neural progenitors using a conditional Nestin-Cre; p75NTR floxed mouse causes increased apoptosis of progenitor cells. By E14.5, the number of Tbr2-positive progenitor cells was significantly reduced and the rate of neurogenesis was halved. Furthermore, in adult knockout mice, there were fewer cortical pyramidal neurons, interneurons, cholinergic basal forebrain neurons, and striatal neurons, corresponding to a relative reduction in volume of these structures. Thalamic midline fusion during early postnatal development was also impaired in Nestin-Cre p75NTR floxed mice, indicating a novel role of p75NTR in the formation of this structure. The phenotype of this strain demonstrates that p75NTR regulates multiple aspects of brain development, including cortical progenitor cell survival, and that expression during early neurogenesis is required for appropriate formation of telencephalic structures.