Early Pattern Formation Research Articles

Multiple Hox/ HOM-Class Homeoboxes in Platyhelminthes

The importance of the Hox/ HOM class of homeobox genes in early anterior-posterior pattern formation and the conserved genomic organization of this gene family provides an interesting study in genome evolution. The Platyhelminthes (flatworms) are a basal metazoan group with a simple bilateral body plan. We used the polymerase chain reaction (PCR) to detect Hox/ HOM-class homeobox genes from species representing two classes of flatworms. Seven planarian and five trematode Hox/ HOM-class homeoboxes were found. The sequences of the genes are consistent with the presence of one Hox/ HOM-type cluster in the flatworms. Further analysis of this putative cluster may be expected to provide outgroup information for studying the evolution of the Hox/ HOM clusters in the higher metazoa.

Balanced translocation 12/13 and situs abnormalities: Homology of early pattern formation in man and lower organisms?

Studies in "lower" organisms have identified a set of homologous sequences expressed in oocytes and early embryos that is critical for pattern formation. Mutations in such genes may exhibit maternal effect--they cause abnormalities in the fetus only when present in the mother. We report on a mother and child with identical, apparently balanced translocations having the breakpoints 12q13.1 and 13p13. The fetus had multiple anomalies including bilateral trilobar lungs, complex heart defect, malrotation of the gut, and asplenia, while the mother was entirely normal. Several hypotheses are advanced to explain this variable expression including transection of a gene with maternal effect--lateral asymmetry in the fetus is influenced by the maternal genotype. This explanation would account for the higher transmission of congenital heart disease to offspring by affected females noted in several studies. The human counterparts of 2 loci (int-1 and HOX 3) involved in Drosophila early pattern formation are located near the translocation breakpoint 12q13.1. If one of these genes is responsible for situs abnormality, then university of positional code (but not of embryologic mechanism) is suggested for higher metazoans.

Bifurcation of the amphibian embryo's axis: analysis of variation in response to egg centrifugation.

Xenopus embryos have been reported to vary widely in their developmental response to centrifugation. Variation in response to centrifugation, as measured by embryo survival and twinning of axial structures, was monitored different spawnings of Xenopus laevis eggs. A convenient method for quantifying the egg cytoplasm's potential for displacement in a centrifugal field was employed. It involved testing small batches of eggs from each spawn under carefully controlled conditions for displacement of the cytoplasm while held in an inverted orientation. The cytoplasmic immobility (CIM) values thus measured in samples from each spawn were correlated with the spawning's developmental success (survival of embryos) and the twinning frequency after centrifugation. Those spawnings with high CIM values (i.e. a rigid or stiff cytoplasm) had the highest survival rates and the lowest frequency and severity of twinning in centrifuged eggs. Variations in CIM account for the broad variation in response to centrifugation previously noted in several reports and further emphasize the role cytoplasmic compartments play vis-à-vis egg organization and early embryonic pattern formation.

Morphogenesis and Evolution

In the preceding chapters we have built up the premises of an argument concerning morphogenesis and evolution. These are as follows: 1.Evolution occurs through processes of introduction and sorting of variation. 2.In a genealogical hierarchy, introduction and sorting of variation can occur at a series of focal levels and it is a property of the hierarchy that there is upward and downward causation between focal levels. 3.The crucial role of developmental processes with respect to evolutionary mechanisms is in the causation of new phenotypes. Phenotypes are always expressed in individual organisms, but the properties of other focal levels in the genealogical hierarchy must also be considered. 4.Development is also essentially hierarchical, involving processes acting at different focal levels. Each level is defined as the place where new gene expression occurs. For simplicity we can divide its hierarchy into stages from early pattern formation to late cytodifferentiation, each including unknown (but very large) numbers of phases of new gene expression. It must be noted that ontogeny of a given individual or given taxon represents a route through the basic hierarchy of developmental stages that, through historical accident or selective bias, may be extremely convoluted and unpredictable. 5.In the systematics of any group, there is a general correlation between taxonomic rank and different grades or ranks of morphological characters. There is a series of levels or grades of generality of phenotypic characters caused at different levels of the morphogenetic hierarchy. 6.The morphogenetic hierarchy that produces the different grades of phenotypic morphology can potentially involve upward but little if any downward causation. 7.The course of evolution appears principally to produce clusters of evolutionarily equivalent species rather than lines of progressive change. At any taxonomic level, diversification within a group has therefore to be distinguished from those rarer phases of progressive evolution leading to establishment of new groups. The two involve quite different processes because they involve the morphogenetic causation of different levels of morphological characters. 8.Phenotypic characters may occur in groups that are linked both in the sense of functional integration of the phenotype itself and/or by virtue of the integration and interdependency of developmental pathways in morphogenesis.

Brief cytochalasin-induced disruption of microfilaments during a critical interval in 1-cell C. elegans embryos alters the partitioning of developmental instructions to the 2-cell embryo

We are investigating the involvement of the microfilament cytoskeleton in the development of early Caenorhabditis elegans embryos. We previously reported that several cytoplasmic movements in the zygote require that the microfilament cytoskeleton remain intact during a narrow time interval approximately three-quarters of the way through the first cell cycle. In this study, we analyze the developmental consequences of brief, cytochalasin D-induced microfilament disruption during the 1-cell stage. Our results indicate that during the first cell cycle microfilaments are important only during the critical time interval for the 2-cell embryo to undergo the correct pattern of subsequent divisions and to initiate the differentiation of at least 4 tissue types. Disruption of microfilaments during the critical interval results in aberrant division and P-granule segregation patterns, generating some embryos that we classify as 'reverse polarity', 'anterior duplication', and 'posterior duplication' embryos. These altered patterns suggest that microfilament disruption during the critical interval leads to the incorrect distribution of developmental instructions responsible for early pattern formation. The strict correlation between unequal division, unequal germ-granule partitioning, and the generation of daughter cells with different cell cycle periods observed in these embryos suggests that the three processes are coupled. We hypothesize that (1) an 'asymmetry determinant', normally located at the posterior end of the zygote, governs asymmetric cell division, germ-granule segregation, and the segregation of cell cycle timing elements during the first cell cycle, and (2) the integrity or placement of this asymmetry determinant is sensitive to microfilament disruption during the critical time interval.

Expression and function of the segmentation gene fushi tarazu during Drosophila neurogenesis.

Segmentation genes control cell identities during early pattern formation in Drosophila. One of these genes, fushi tarazu (ftz), is now shown also to control cell fate during neurogenesis. Early in development, ftz is expressed in a striped pattern at the blastoderm stage. Later, it is transiently expressed in a specific subset of neuronal precursor cells, neurons (such as aCC, pCC, RP1, and RP2), and glia in the developing central nervous system (CNS). The function of ftz in the CNS was determined by creating ftz mutant embryos that express ftz in the blastoderm stripes but not in the CNS. In the absence of ftz CNS expression, some neurons appear normal (for example, the aCC, pCC, and RP1), whereas the RP2 neuron extends its growth cone along an abnormal pathway, mimicking its sibling (RP1), suggesting a transformation in neuronal identity.

Lithium-induced respecification of pattern in Xenopus laevis embryos

Much interest in vertebrate embryology is now focused on early pattern formation in the frog, Xenopus laevis. In this species, the body plan is specified by a stable positional system set up by a cytoplasmic rotation in the zygote that occurs before first cleavage. Perturbation of this initial cellular event by a variety of means causes permanent distortions of the positional system. Until now it has not been possible to alter the positional system after it has been specified. However, we report here that lithium, when applied after specification of the body plan, can respecify the positional system of the Xenopus embryo such that dorsal, axial structures develop from cells that otherwise contribute to ventral structures. Lithium is usually considered to have negative effects on early embryo development, but our results show that lithium can act in a positive manner to produce structures which represent the uppermost values of the positional system. This discovery introduces a convenient means to study cellular and molecular mechanisms of early vertebrate pattern expression.

The Dynamics of Early Pattern Formation in Amphibian Embryogenesis

Prior to first cleavage the dorsal/ventral polarity of the amphibian egg is established. That polarity can be altered by ultraviolet irradiation. Although embryos irradiated with low doses of UV apparently develop normally through gastrulation, various defects in neural morphogenesis become apparent. Among these defects are abnormalities in the structure of the notochord. In some embryos the notochord is partially defective, while in others it is completely lacking. Detailed analyses of those embryos with the scanning electron microscope generated novel interpretations concerning the role of the notochord in early pattern formation.