REGULATION OF THE XENOPUS LABIAL HOMEODOMAIN GENES, HOXA1 AND HOXD1 -ACTIVATION BY RETINOIDS AND PEPTIDE GROWTH-FACTORS

Vertebrate homologues of Drosophila labial are likely to play key role s in anteroposterior axis formation. However, little is known about th e regulation of these genes during vertebrate development. Here we exa mine the expression and regulation of the Xenopus labial homeodomain g enes, HoxA1 and HoxD1. HoxA1 was expressed around the dorsoventral cir cumference of the trunk in neurula embryos, with later expression in s pinal cord, midbrain, hindbrain, and endolymphatic duct. By mid gastru la, HoxD1 was predominantly expressed in dorsolateral and ventral ecto derm, with a gap in expression at the dorsal midline. By neurula, vent ral expression had declined with most expression restricted to dorsola teral mesoderm and ectoderm. Retinoic acid strongly induced HoxA1 and HoxD1 throughout the ectoderm and mesendoderm of gastrula stages, whil e in older embryos retinoids induced ectopic expression of these genes in more limited regions. Induction by retinoids was independent of pr otein synthesis. Surprisingly, HoxA1 was expressed at high levels in i solated animal caps in the absence of retinoic acid. The peptide growt h factors bFGF and activin A strongly induced expression of HoxD1, but not HoxA1, in animal caps; however, RNA accumulated only many hours a fter the application of these factors. Overexpression of thyroid hormo ne receptor (c-erbA) prevented induction of HoxD1 by retinoic acid in animal caps. c-erbA also ablated expression of HoxD1 in whole embryos, suggesting a role for endogenous retinoids in the regulation of HoxD1 expression. Dominant interfering activin and FGF receptors prevented expression of HoxD1 in vivo, implicating these factors in the normal i nduction of HoxD1. Our data indicate that induction of labial-like hom eodomain genes is complex and may require many factors. (C) 1995 Acade mic Press, Inc.