Hox3 genes coordinate mechanisms of genetic suppression and activation in the generation of branchial and somatic motoneurons

Abstract

In the developing hindbrain, the functional loss of individual Hox genes has revealed some of their roles in specifying rhombomere (r) identity. However, it is unclear how Hox genes act in concert to confer the unique identity to multiple rhombomeres. Moreover, it remains to be elucidated how these genes interact with other transcriptional programs to specify distinct neuronal lineages within each rhombomere. We demonstrate that in r5, the combined mutation of Hoxa3 and Hoxb3 result in a loss of Pax6- and Olig2-expressing progenitors that give rise to somatic motoneurons of the abducens nucleus. In r6, the absence of any combination of the Hox3 paralogous genes results in ectopic expression of the r4-specific determinant Hoxb1. This ectopic expression in turn results in the differentiation of r4-like facial branchiomotoneurons within this rhombomere. These studies reveal that members of the Hox1 and Hox3 paralogous groups participate in a 'Hox code' that is necessary for coordinating both suppression and activation mechanisms that ensure distinction between the multiple rhombomeres in the developing hindbrain.

Retinoic acid influences anteroposterior positioning of epidermal sensory neurons and their gene expression in a developing chordate (amphioxus)

“…Recent work on the developing vertebrate hindbrain and spinal cord have demonstrated a role for Hox genes in subdividing larger neuronal populations into neuronal subtypes (51)(52)(53)(54). Our present results show that four amphioxus Hox genes and two neuronal differentiation genes (amphioxus islet and AmphiERR) are expressed in nonoverlapping patterns in different epidermal sensory neurons.…”

Epigenetic regulations in hematopoietic Hox code

“…There are no dramatic alterations in morphogenesis caused by mutations of a single Hox gene in vertebrate. For example, Hoxa3, Hoxb3, and Hoxd3 generally have very similar patterning, and gene targeting has shown that members of paralogue group 3 functionally compensate for each other when one paralogous gene is disrupted Capecchi, 1997, 1998;Gaufo et al, 2003). However, mice with conditional knockout of all nine HoxC genes die at birth, suggesting that genes in each Hox cluster are collectively necessary for the development of mice (Suemori and Noguchi, 2000).…”

Induction of a Parafacial Rhythm Generator by Rhombomere 3 in the Chick Embryo

“…Local changes in anteroposterior Hox patterns (Brunet and Ghysen, 1999;Dominguez del Toro et al, 2001) as well as in the interaction of Hox genes with dorsoventral establishment of neuronal diversity (Simon et al, 1995;Gaufo et al, 2003;Pattyn et al, 2003) may offer novel opportunities for the evolution of distinct subsets of neurons and the emergence of novel functions. We have now identified a robust developmental specification mechanism that is instructive for the maturation of the activity pattern of hindbrain neuronal circuits.…”