Differentiation of Sensory Neuron Lineage During the Late First and Early Second Trimesters of Human Foetal Development

Abstract

Sensory neurons within DRGs are broadly divided into three types that transmit nociceptive, mechanical, and proprioceptive signals. These subtypes are established during in utero development when sensory neurons differentiate into distinct categories according to a complex developmental plan. Most of what we know about this developmental plan comes from studies in rodents and little is known about this process in humans. The present study documents the expression of key genes involved in human sensory neuron development during the late first and early second trimesters (9-16WG). We observed a decrease in the expression of SOX10 and BRN3A, factors associated with migration and proliferation of sensory neurons, towards the end of the first trimester. Small and large sensory neuron populations also emerged at the end of the first trimester, as well as the transcription factors responsible for defining distinct sensory neuron types. NTRK1, which is expressed in nociceptive neurons, emerged first at ~11 WG followed by NTRK2 in mechanoreceptors at ~12 WG, with NTRK3 for proprioceptors peaking at ~14 WG. These peaks were followed by increased expression of their respective neurotrophic factors. Our results show significant differences in the expression of key signalling molecules for human DRG development versus that of rodents, most notably the expression of neurotrophins that promote the survival of sensory neuron types. This highlights the importance of examining molecular changes in humans to better inform the application of data collected in pre-clinical models.

Keywords: development; nociceptors; sensory neurons; transcription factors.