The branchial Hox code and its implications for gene regulation, patterning of the nervous system and head evolution.
In this study we have examined the expression of murine Hox homeobox containing genes by in situ hybridisation in the branchial region of the head. Genes from the Hox complexes display segmentally restricted domains of expression in the developing hindbrain, which are correlated with similar restricted domains in the neural crest and surface ectoderm of the branchial arches. Comparison of related genes from the different clusters shows that subfamily members are expressed in identical rhombomeres and branchial arches. These patterns suggest a combinatorial system for specifying regional variation in the head, which we refer to as a Hox code. The Hox genes also display dynamic dorso-ventral (D-V) restrictions in the developing neural tube which mirror the timing and spatial distributions of the birth of major classes of neurons in the CNS. Genes in the Hox-2 cluster all have a similar D-V distribution that differs from that of genes from the other Hox clusters, and suggests that members of a subfamily may be used to specify positional values to different subsets of cells at the same axial level. These results are discussed in terms of a system for patterning the branchial regions of the vertebrate head, and evolution of head structures. We have also examined aspects of the transcriptional regulation of Hox-2 genes in transgenic mice using a lacZ reporter gene. We have been able to reconstruct the major pattern of the Hox-2.6 gene on the basis of identical expression of the transgene and the endogenous gene with respect to timing, spatial restrictions and tissue-specific distributions. Deletion analysis has enabled us to identify three regions involved in generating this pattern. Two of these regions have the properties of enhancers which are capable of imposing spatially-restricted domains of expression on heterologous promoters. We have generated similar Hox-lacZ fusions that reconstruct the highly restricted patterns of the Hox-2.1 and Hox-2.8 genes in the developing nervous system, supporting our in situ analysis and the idea of a Hox code. These transgenic experiments are a useful step in examining regulation in the Hox cascade.
Lab of Eukaryotic Molecular Genetics, MRC-National Institute for Medical Research, Mill Hill, London, UK.
P
P
Hunt
J
J
Whiting
S
S
Nonchev
M H
MH
Sham
H
H
Marshall
A
A
Graham
M
M
Cook
R
R
Allemann
P W
PW
Rigby
M
M
Gulisano
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D001934:Branchial Region / Q000502:physiology; D017124:Conserved Sequence; D004330:Drosophila / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D005801:Genes, Homeobox / Q000235:genetics*; D005815:Genetic Code; D006257:Head / Q000196:embryology*; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics; D009420:Nervous System / Q000196:embryology*; D017386:Sequence Homology, Amino Acid