Contribution of Hox genes to the diversity of the hindbrain sensory system

Abstract

The perception of environmental stimuli is mediated through a diverse group of first-order sensory relay interneurons located in stereotypic positions along the dorsoventral (DV) axis of the neural tube. These interneurons form contiguous columns along the anteroposterior (AP) axis. Like neural crest cells and motoneurons, first-order sensory relay interneurons also require specification along the AP axis. Hox genes are prime candidates for providing this information. In support of this hypothesis, we show that distinct combinations of Hox genes in rhombomeres (r) 4 and 5 of the hindbrain are required for the generation of precursors for visceral sensory interneurons. As Hoxa2 is the only Hox gene expressed in the anterior hindbrain(r2), disruption of this gene allowed us to also demonstrate that the precursors for somatic sensory interneurons are under the control of Hox genes. Surprisingly, the Hox genes examined are not required for the generation of proprioceptive sensory interneurons. Furthermore, the persistence of some normal rhombomere characteristics in Hox mutant embryos suggests that the loss of visceral and somatic sensory interneurons cannot be explained solely by changes in rhombomere identity. Hox genes may thus directly regulate the specification of distinct first-order sensory relay interneurons within individual rhombomeres. More generally, these findings contribute to our understanding of how Hox genes specifically control cellular diversity in the developing organism

Lbx1 Acts as a Selector Gene in the Fate Determination of Somatosensory and Viscerosensory Relay Neurons in the Hindbrain

“…stance, in HoxB1 and HoxA3/HoxB3 mutant mice, a population of Phox2b/Lmx1b dorsal neurons likely to correspond to viscerosensory relay neurons assume an aberrant fate and express Lbx1 in rhombomeres 4 and 5, respectively (Gaufo et al, 2004). The rhombomeres retained some normal characteristics in the mutants, indicating that these fate changes cannot be attributed solely to changes in rhombomere identity.…”

Epigenetic regulation in neural crest development

“…NCCs of the posterior midbrain and rhombomeres migrate via three streams into pharyngeal arches (Fig. 2B), where they will give rise to a number of cranial structures, such as neurons, glia, jaws, and other front skull bones (reviewed in Trainor, 2003;Briscoe and Wilkinson, 2004;Gaufo et al, 2004). Posterior midbrain-derived, r1-derived, and r2-derived NCCs that colonize PA1 are devoid of Hox expression (Hox-free).…”

Preservation of segmental hindbrain organization in adult frogs

“…The likelihood that many adult hindbrain nuclei will retain the rhombomeric pattern is supported by the demonstration that distinct alar plate neuronal types are specified by segmentally regulated Hox gene expression (Gaufo et al, 2004) and by the spatial continuity of individual rhom-bomeres throughout development shown in surgical fatemapping studies (Marín and Puelles, 1995;Wingate and Lumsden, 1996;Cambronero and Puelles, 2000). An initial test of rhombomeric mapping of adult vestibular organization was performed by transposing the rostrocaudal stereotactic coordinates of physiologically identified second-order semicircular canal and otolith neurons onto a preliminary version of the rhombomeric map presented in the current study (Straka et al, , 2003.…”