Hoxa1 and Krox-20 synergize to control the development of rhombomere 3.
The transcription factor genes Hoxa1 and Krox-20 have been shown to play important roles in vertebrate hindbrain segmentation. In this report, we present evidence for novel functions of these genes which co-operate in specifying cellular identity in rhombomere (r) 3. Although Hoxa1 has not been observed to be expressed rostrally to the prospective r3/r4 boundary, its inactivation results in (i) the appearance of patches of cells presenting an r2-like molecular identity within r3, (ii) early neuronal differentiation in r3, normally characteristic of even-numbered rhombomeres, and (iii) abnormal navigation of r3 motor axons, similar to that observed in even-numbered rhombomeres. These phenotypic manifestations become more severe in the context of the additional inactivation of one allele of the Krox-20 gene, demonstrating that Hoxa1 and Krox-20 synergize in a dosage-dependent manner to specify r3 identity and odd- versus even-numbered rhombomere characters. In addition, these data suggest that the control of the development of r3 may not be autonomous but dependent on interactions with Hoxa1-expressing cells.
Helmbacher
F
F
Unité 368 de l'Institut National de la Santé et de la Recherche Médicale, Ecole Normale Supérieure, 75230 Paris Cedex 05, France.
Pujades
C
C
Desmarquet
C
C
Frain
M
M
Rijli
F M
FM
Chambon
P
P
Charnay
P
P
D000818:Animals; D001369:Axons / Q000502:physiology; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051767:Early Growth Response Protein 2; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009046:Motor Neurons / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D016133:Polymerase Chain Reaction; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016335:Zinc Fingers; D000099261:Homeobox A1 Protein
D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; D018398:Homeodomain Proteins; D014157:Transcription Factors; D000099261:Homeobox A1 Protein; C497327:Egr2 protein, mouse