Expression and interactions of the two closely related homeobox genes <i>Phox2a</i> and <i>Phox2b</i> during neurogenesis

TLDR

Homeobox transcription factors, such as Phox2a, are expressed in differentiating neurons of the autonomic nervous system and hindbrain motor nuclei and are thought to control neuronal generation and survival. The study characterizes Phox2b, a close relative of Phox2a, to investigate its expression pattern and role in the autonomic nervous system. Phox2b is co‑expressed with Phox2a, precedes it in hindbrain development, and its loss in Phox2a‑deficient mice indicates positive cross‑regulation; targeted deletion of Phox2a disrupts the locus coeruleus, visceral sensory and parasympathetic ganglia, and cranial nerve nuclei, highlighting a broader role for Phox2 genes in autonomic and cranial motor specification.

Abstract

ABSTRACT Recent evidence suggests that specific families of homeo-domain transcription factors control the generation and survival of distinct neuronal types. We had previously char-acterized the homeobox gene Phox2a, which is expressed in differentiating neurons of the central and peripheral autonomic nervous system as well as in motor nuclei of the hindbrain. Targeted deletion of the Phox2a gene affects part of the structures in which it is expressed: the locus coeruleus, visceral sensory and parasympathetic ganglia and, as we show here, the nuclei of the IIIrd and IVth cranial nerves. We now report on the characterization of Phox2b, a close relative of Phox2a, with an identical homeo-domain. Phox2a and Phox2b are co-expressed at most sites, therefore suggesting a broader role for Phox2 genes in the specification of the autonomic nervous system and cranial motor nuclei than revealed by the Phox2a knock-out mice. A detailed analysis of the relative timing of Phox2a and Phox2b expression at various sites suggests positive cross-regulations, which are substantiated by the loss of Phox2b expression in cranial ganglia of Phox2a-deficient mice. In the major part of the rhombencephalon, Phox2b expression precedes that of Phox2a and starts in the proliferative neu-roepithelium, in a pattern strikingly restricted on the dorsoventral axis and at rhombomeric borders. This suggests that Phox2b links early patterning events to the differentiation of defined neuronal populations in the hindbrain.