Anterior Central Nervous System Research Articles

Landmarks in the anterior central nervous system of amphioxus larvae

The anterior end of the dorsal nerve cord of amphioxus is described at the 3-4 gill slit stage based on serial transmission electron microscopy and three-dimensional reconstruction, with special attention to structures that are potential landmarks for comparing amphioxus with other chordates. The larval nerve cord is divisible, at approximately the level of the first somite, into a short anterior region, the cerebral vesicle (c.v.), and an extended posterior region that is thought to include homologues of the vertebrate hindbrain and spinal cord. The c.v., in turn, has an anterior part with a tubular neural canal and a posterior part with a keyhole-shaped neural canal similar to that found in the rest of the cord. The junction between these two parts of the c.v. is marked by a cluster of infundibular cells. The anterior c.v., whose cells have cilia that point anteriorly, includes (i) a structure we call the frontal eye, consisting of a pigment spot and transverse rows of putative receptor and nerve cells, and (ii) several small ventral commissures bridging the major nerve tracts that run ventrolaterally along either side of the nerve cord. The posterior c.v., in contrast, contains cells whose cilia point posteriorly, and includes (i) the beginnings of the floorplate, which continues posteriorly through the rest of the nerve cord, (ii) the dorsal lamellar body, made up of cells with cilia that expand into flattened lamellae, and (iii) a large ventral commissure that incorporates fibres arising from cells of the lamellar body. Where probable homologues of c.v. structures can be identified in vertebrate brain, they are found in the diencephalon, which suggests the c.v. and the vertebrate diencephalon are, to a degree, homologous.

A Drosophila homologue of human Sp1 is a head-specific segmentation gene.

Segmentation in Drosophila is based on a cascade of hierarchical gene interactions initiated by maternally deposited morphogens that define the spatially restricted domains of gap gene expression at blastoderm (reviewed in ref. 1). Although segmentation of the embryonic head is morphologically obscured, the repeated patterns of expression of the segment polarity genes reflect the formation of seven head segments; two of these depend on the segmentation and homeotic genes used in the trunk, whereas the others form as a result of the activity of the head-specific genes orthodenticle (otd), empty spiracles (ems) and buttonhead (btd). The genes ems and otd encode homeodomain proteins, suggesting that they may function as transcription factors. They are expressed in overlapping stripes in the early embryonic head of Drosophila, and their vertebrate homologues, otx and emx, are expressed in overlapping domains in the anterior central nervous system of the mouse embryo. We show here that btd is expressed in a stripe covering the head analgen of the segments affected in btd lack-of-function mutants and that btd encodes a zinc-finger-type transcription factor with sequence and functional similarity to the prototype mammalian transcription factor Sp1 (ref. 9). When expressed in the spatial pattern of btd, a transgene providing Sp1 activity can support development of the mandibular segment in the head of btd mutant embryos. A ubiquitous transcription factor from humans can therefore replace an essential component of the genetic circuitry required to specify the development of a particular head segment in the fly.

XASH1, a Xenopus homolog of achaete-scute: a proneural gene in anterior regions of the vertebrate CNS

The pro-neural achaete-scute complex (ASC) of Drosophila encodes four homologous proteins, each containing a basic helix-loop-helix (bHLH) domain, characteristic of a large family of transcription factors. We have isolated XASH1, a Xenopus homolog of achaete-scute. The XASH1 protein is very similar to the ASC proteins of Drosophila and the rat homolog, MASH1. XASH1 is expressed in the embryonic anterior central nervous system in a dynamic sequence, first in the midbrain, then in the forebrain, and then in the eye and hindbrain. In the larva, XASH1 expression correlates with regions of continued neurogenesis in the CNS, revealing the pattern of rhombomeres in the hindbrain, and other proliferative zones in the eye and midbrain. As a heterodimer with the bHLH protein E12, XASH1 binds specifically to an enhancer sequence derived from the promoter of the proneural achaete gene of Drosophila. This binding is inhibited by the extramacrochaete protein, a negative regulator of ASC gene function and neurogenesis in Drosophila. The combined evidence described in this paper strongly suggests that XASH1 plays a role in Xenopus neurogenesis similar to that played by the ASC genes in Drosophila.

Induction of a RAR beta 2-lacZ transgene by retinoic acid reflects the neuromeric organization of the central nervous system.

The hormone retinoic acid (RA) has been implicated in the organization of the anteroposterior (AP) body axis. In this paper, we describe the effects of RA on the activity of the RA-inducible retinoic acid receptor-beta 2 (RAR beta 2) promoter. When transgenic embryos carrying a RAR beta 2-lacZ reporter gene were exposed to a single dose of RA between gestational days 8.5 to 10.5, lacZ expression was induced in the anterior central nervous system (CNS). Strikingly, the transgene was expressed in a segmented pattern reminiscent of that of Drosophila 'pair-rule' genes. RA treatment of midgastrulation embryos at day 7.5 disturbed the segmentation and produced severe craniofacial defects. We discuss the possibility that the entire anterior CNS is segmented and that this segmentation is reflected by the RAR beta 2-lacZ induction pattern.

The midbrain-hindbrain phenotype of [formula omitted] mice results from stepwise deletion of engrailed-expressing cells by 9.5 days postcoitum

Mice homozygous for null alleles of the putative signaling molecule Wnt-1 have a reproducible phenotype: loss of the midbrain and adjacent cerebellar component of the metencephalon. By examining embryonic expression of the mouse engrailed (En) genes, from 8.0 to 9.5 days postcoitum, we demonstrate that Wnt-1 primarily regulates midbrain development. The midbrain itself is required for normal development of the metencephalon. Thus, the observed neonatal phenotype is explained by a series of early events, within 48 hr of neural plate induction, that leads to a complete loss of En domains in the anterior central nervous system. Wnt-1 and a related gene, Wnt-3a, are coexpressed from early somite stages in dorsal aspects of the myelencephalon and spinal cord. We suggest that functional redundancy between these two genes accounts for the lack of a caudal central nervous system phenotype.

Retinoic acid modifies the pattern of cell differentiation in the central nervous system of neurula stage Xenopus embryos

Neural cell markers have been used to examine the effect of retinoic acid (RA) on the development of the central nervous system (CNS) of Xenopus embryos. RA treatment of neurula stage embryos resulted in a concentration-dependent perturbation of anterior CNS development leading to a reduction in the size of the forebrain, midbrain and hindbrain. In addition the overt segmental organization of the hindbrain was abolished by high concentrations of RA. The regional expression of two cell-specific markers, the homeobox protein Xhox3 and the neurotransmitter serotonin was also examined in embryos exposed to RA. Treatment with RA caused a concentration-dependent change in the pattern of expression of Xhox3 and serotonin and resulted in the ectopic appearance of immunoreactive neurons in anterior regions of the CNS, including the forebrain. Collectively, our results extend previous studies by showing that RA treatment of embryos at the neurula stage inhibits the development of anterior regions of the CNS while promoting the differentiation of more posterior cell types. The relevance of these findings to the possible role of endogenous retinoids in the determination of neural cell fate and axial patterning is discussed.

Prospective Neural Areas and their Morphogenetic Movements during Neural Plate Formation in the Xenopus Embryo. II. Disposition of Transplanted Ectoderm Pieces of X. borealis Animal Cap in Prospective Neural Areas of Albino X. laevis gastrulae.: (developmental fate/neural plate area/Xenopus embryo/chimera/quinacrine).

Small pieces of the animal cap of X. borealis gastrulae were transplanted into various regions of the noninvoluting marginal zone of albino X. laevis gastrulae, and the distribution of the donor cells was analyzed by quinacrine fluorescence staining. The present study indicated that the prospective central nervous system (CNS) lies as a belt-shaped area in the noninvoluting marginal zone of early gastrulae. This belt-shaped prospective neural area extends as far as 0.7 mm (115° to the vegetal pole) above the blastopore in the dorsal midline and 1.3 mm lateral (130° to the dorsal midline) to the dorsal midline. The ectoderm of the dorsal region extends in the animal-vegetal direction and forms the ventral side of the CNS. The dorsalateral and lateral regions converge toward the dorsal midline and extended in the animal-vegetal direction. The former constitutes the lateral side of the anterior CNS, and the latter the dorso-lateral side of the posterior CNS. The outer layer of ectoderm which was transplanted onto the inner layer of the host gastrula differentiated into neural tissues. The prospective areas of the CNS and their morphogenetic movement during Xenopus embryogenesis are also discussed with regard to neural induction.

Bilateral symmetry in the mediation of circadian differences in earthworms

The rates of locomotion and light-withdrawal of earthworms, Lumbricus terrestris L., in which one circumpharyngeal connective had been severed were compared with those of normal worms during test-periods which started at 12:00 and 20:00, E.S.T. Normal worms withdrew from light and crawled faster during the evening hours than at midday. The animals in which the connective had been cut performed at essentially the same rates during the noon and evening periods. Data presented in the table show the similarity between the results of this investigation and those of earlier studies on brainless worms and on Lumbricus in which both circumpharyngeal connectives were cut (Bennett, 1967). The new findings support the earlier conclusion that an intact anterior central nervous system is necessary for the mediation of circadian differences in earthworms, and indicate that the regulating mechanism of the temporal differences is one which demands the participation of neural units of both sides of the anterior central nervous system.