evolution of dorsoventral pattern formation in the chordate neural tube, The

The Evolution of Dorsoventral Pattern Formation in the Chordate Neural Tube1

SYNOPSIS. Living members of Phylum Chordata are divided into three groups: the Urochordata, the Cephalochordata (amphioxus) and the Craniata (vertebrates). These animals are united by a common body plan, a key component of which is the development of a neural tube dorsal to a notochord. Studying the genetics and embryology of these animals allows evolutionary comparison to be made between the mechanisms controlling the development of homologous body parts in different taxa. This paper focuses specifically on the evolution of dorsoventral pattern in the neural tube. In vertebrate embryos external inductive signals, originating from the notochord and the dorsal ectoderm, initiate a program of cell differentiation that subdivides the neural tube into a stereotyped pattern of neurons and glia. To understand the evolution of this pattern I have been characterising amphioxus members of the gene families involved, including genes from the HNF-3, Msx, Hh, Gli and Netrin families. Coupled with similar analyses of urochordate development, analysis of these genes shows that the signalling functions of the notochord and lateral ectoderm seem to predate vertebrate origins, and have not increased in complexity in vertebrates despite duplication of the gene families involved. Conversely, expansion of gene families downstream of these signals has increased the complexity of gene expression and function in vertebrate embryos. These data therefore provide an indication of how gene duplication and divergence may have provided the raw material for the evolution of the complex pattern of cell types that develops in the vertebrate neural tube.

INTRODUCTION

Vertebrates share Phylum Chordata with two other living taxa, the Urochordata (ascidians and relatives) and the Cephalochordata (amphioxus), known collectively as the protochordates. These taxa are united by the possession of a rod-like mesodermal notochord and a dorsal, hollow neural tube, both key features of the chordate body plan. The neural tube of chordates develops from a sheet of ectoderm known as the neural plate. Typically the neural plate forms the neural tube by a "rolling up" process, although some chordates develop a neural tube exclusively by cavitation. The later, however, is considered a derived character. During the development of the vertebrate neural tube a precise pattern of cell differentiation is established. Along the dorsoventral axis this leads to the positioning of specific cell types in stereotypic locations and, while the pattern that develops shows some differences between different vertebrate taxa, a general underlying theme is apparent; for instance motor neurons develop in the ventral neural tube while sensory neurons and neural crest cells develop in the dorsal neural tube (Butler and Hodos, 1996).

The cellular and molecular mechanisms which control the development of this pattern have been the subject of intense scrutiny in recent years. In particular, tissues adjacent to the neural tube (the notochord to the ventral and the lateral ectoderm to the dorsal) have been implicated in the initial control of dorsoventral pattern. In all chordates the notochord lies ventral to the neural tube and expresses a number of transcription factor genes, including those of the HNF-3 class which encode fork head domain proteins (Lai et al., 1991; Dirksen and Jamrich, 1992; Ruiz i Altaba and Jessell, 1992). Notochord cells also express members of the hedgehog (Hh) family of cell signalling molecules, most importantly Sonic hedgehog (Shh) (Echelard et al., 1993; Krauss et al., 1993; Currie and Ingham, 1996). In amniotes, contact between hedgehog-secreting cells of the notochord and naive neurectoderm leads to the induction of a specific cell population known as the floor plate at the ventral midline of the neural plate (Placzek et al., 1993; Echelard et al., 1993; Roelink et al., 1994, 1995). Floor plate cells activate expression of both HNF-3 and Shh and can also be recognised by the expression of other markers, such as F-spondin and Netrin (Klar et al., 1992; Kennedy et al., 1994). Throughout subsequent development floor plate cells retain a characteristic non-neuronal morphology and have a critical role in axon guidance.

The induction of dorsal cell types occurs in an analogous manner. Dorsal signals initially derive from adjacent lateral ectoderm and are mediated by members of the Tgf(beta) family, particularly those of the Bmp2/4 and Bmp-5/6/7/8 types (Liem et al., 1995; Takahashi et al., 1996). In the chick embryo at least one member of each type (Bmp-4 and Bmp-7) are expressed in the lateral ectoderm and studies have suggested that Bmp-2/4 and Bmp-5/6/7/8 molecules may hetero- as well as homodimerise (Liem et al., 1995; Lyons et al., 1995). Bmp signalling from the ectoderm induces the expression of multiple Bmp genes in the dorsal neural tube, in conjunction with the expression of other markers such as transcription factors of the Msx and snail families (Liem et al., 1995; Shimeld et al., 1996; Takahashi et al., 1996). At the cellular level this results in the development of dorsal cell types such as sensory neurons and neural crest in the dorsal neural tube.