The Expression Pattern of the Transcription Factor Phox2 Delineates Synaptic Pathways of the Autonomic Nervous System

TLDR

Transcription factors, especially homeodomain proteins, are expressed in specific neuronal groups during development, yet how they control neural identity remains largely unknown, though Phox2 has been shown to be expressed exclusively in differentiated neurons or their precursors and to correlate with dopamine‑beta‑hydroxylase. We confirmed this correlation at the single‑cell level using an anti‑Phox2 antibody. We also found that many Phox2‑positive cells participate in or reside within synaptic circuits of medullary autonomic reflexes, suggesting Phox2 may help establish these circuits.

Abstract

Many transcription factors, and most prominently among them, homeodomain proteins, are expressed in specific groups of cells in the developing nervous system in patterns that suggest their involvement in neural fate determination. How various aspects of neural identity are controlled by such transcription factors, or sets of them, is still mostly unknown. It has been shown previously that Phox2 is such a homeodomain protein, expressed exclusively in differentiated groups of neurons or their precursors, and that its expression correlated with that of the noradrenaline synthesis enzyme dopamine-beta-hydroxylase. Here we confirm this striking correlation at the single-cell level with the use of an anti-Phox2 antibody. Moreover, we uncover a second, nonmutually exclusive correlative clue to the Phox2 expression pattern: a high proportion of Phox2-expressing cells are involved in, or located in areas involved in, synaptic circuits, i.e., that of the medullary control reflexes of autonomic functions. This suggests that Phox2 could be involved in the establishment of these circuits.