Initiation, establishment and maintenance of Hox gene expression patterns in the mouse.

Spatially and temporally restricted expression of the Hox genes along the main and appendicular axes is essential for correct patterning of vertebrate embryos. In this overview we discuss the latest data that shed light on the mechanisms underlying the generation of the expression domains of the Hox genes. The molecular genetic interactions governing initial transcription of the Hox genes in the posterior part of the primitive streak during mouse and chick gastrulation remain enigmatic. But the recent discovery by Kondo and Duboule (Cell, 97, 1999, 407-417) of a "cluster repressive regulation", will undoubtedly lead to a better understanding of the molecular genetic mechanism underlying colinear and sequential initiation of Hox gene transcription. Recently progress has been booked in characterizing the basal processes driving progression of the Hox expression domains during their establishment. Hox expression is still labile while being established. The transcriptional state of Hox genes in anterior tissues can be reprogrammed under the influence of more posterior locations. Posteriorizing activity may involve RA and FGF signaling. It is only when these interactions and, in some cases at least, regulatory interactions with Hox and cdx gene products occur appropriately, that the Hox expression domains would be correctly established. After the Hox expression domains have been established, regulatory processes involving the products of Polycomb and trithorax- Group genes start operating, perpetuating the transcriptional state of the Hox genes within and outside the expression domains. Whether control at the level of chromatin structure, believed to operate during the late maintenance phase of Hox gene expression, is also involved in regulating concerted initial expression of these genes, is a possibility that has been suggested.

Vertebrate aristaless-related genes.

Aristaless-related genes, a subset of the Paired-related homeobox genes, have in the past few years emerged as a group of regulators of essential events during vertebrate embryogenesis. One group of aristaless-related genes has been linked to the morphogenesis of the craniofacial and appendicular skeleton by their expression patterns and by the phenotypes of natural and artificial mouse mutants. Expression and function in the nervous system characterise a second group, and a third group, the Pitx genes, have been shown to have many different roles, including functions in the pituitary, left-right determination and limb development.