The Origin of a New Progenitor Stem Cell Group in Human Development.

The observation of two precursor groups of the early stem cells (Groups I and II) leads to the realization that a first amount of fetal stem cells (Group I) migrate from the AMG (Aortal-Mesonephric-Gonadal)-region into the aorta and its branching vessels. A second group (Group II) gains quite a new significance during human development. This group presents a specific developmental step which is found only in the human. This continuation of the early development along a different way indicates a general alteration of the stem cell biology. This changed process in the stem cell scene dominates the further development of the human stem cells. It remains unclear where this phylogenetic step first appears. By far not all advanced mammals show this second group of stem cells and their axonal migration. Essentially only primates seem to be involved in this special development.

Cell death as a regulator of cerebellar histogenesis and compartmentation.

Programmed cell death is essential for the homeostasis of tissues and organs. During the development of the central nervous system, programmed cell death is highly regulated and restricted to distinct developmental time points of histogenesis. In this review, we will summarize recent data on the temporal and spatial distribution of programmed Purkinje cell death within the cerebellar cortex. We point out that programmed cell death within distinct regions of the developing cerebellar cortex differs by type and its cellular consequences. We submit the concept that local Purkinje cell death is important for late compartmentation of the cerebellar cortex and its wiring. To support this hypothesis, we provide new data obtained from a cerebellar mutant with prolonged expression of Engrailed-2 specifically in cerebellar Purkinje cells which shows increased local physiological cell death and concomitant changes in the pattern of afferent innervation.

Local desynchronization of cellular development within mammalian male germ cell clones.

Mammalian male germ cells go through the process of spermatogenesis as cell clones. The members of a clone are joined by intercellular bridges which are responsible for synchronizing the spermatogenetic process. The present ultrastructural study on pubertal and adult golden hamster and mouse testes, however, demonstrates that a strict synchronization of germ cell development is not attained by this clonal association in any single instance. Local desynchronization is either indicated by intraclonal divergence at the stage of the cell cycle of the respective germ cells or it is manifested in clones in which single cells are affected by degeneration while other members of the clone are not. The results are discussed with a view to a possible significance of intraclonal desynchronization of male germ cell development in local impairment of spermatogenesis and loss of germ cells.

Physiological purkinje cell death is spatiotemporally organized in the developing mouse cerebellum.

Physiological cell death is crucial for matching defined cellular populations within the central nervous system. Whereas the time course of developmental cell death in the central nervous system is well analyzed, information about its precise spatial patterning is scarce. Yet, the latter one is needed to appraise its contribution to circuit formation and refinement. Here, we document that during normal cerebellar development, dying Purkinje cells were highly localized within the vermal midline and in a lobule specific, parasagittal pattern along the whole mediolateral axis. In addition, single hot spots of cell death localized to the caudal declive and ventral lobule IX within the posterolateral fissure. These hot spots of dying Purkinje cells partly overlapped with gaps within the Purkinje cell layer which supports the classification of different gaps based on histological and molecular criteria, i.e., midline gap, patchy gaps, and raphes. Areas characterized by a high incidence of Purkinje cell death and gaps colocalize with known molecular and functional boundaries within the cerebellar cortex. Physiological cell death can thus be considered to serve as an important regulator of cerebellar histogenesis.

Alopecia and male infertility in oligotriche mutant mice are caused by a deletion on distal chromosome 9.

The recessive mutation oligotriche (olt) affects the coat and male fertility in the mouse. In homozygous (olt/olt) mutants, the coat is sparse, most notably in the inguinal and medial femoral region. In these regions, almost all hair shafts are bent and distorted in their course through the dermis and rarely penetrate the epidermis because the hair cortex is not fully keratinized. During hair follicle morphogenesis, mutant hair follicles exit from anagen one day before those of normal littermates and show a prolongation of the catagen stage. The oligotriche (olt) locus was mapped to distal chromosome 9 within a 5-Mbp interval distal to D9Mit279. Analysis of candidate gene expression revealed that olt/olt mutant mice do not express functional phospholipase C delta 1 (Plcd1) mRNA. This deficiency is the consequence of a 234-kbp deletion involving not only the Plcd1 locus but also the chromosomal segment harboring the genes Vill (villin-like), Dlec1 (deleted in lung and esophageal cancer 1), Acaa1b (acetyl-Coenzyme A acyltransferase 1B, synonym thiolase B), and parts of the genes Ctdspl (carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase-like) and Slc22a14 (solute carrier family 22 member 14). Offspring of olt/olt females, mated with Plcd1 ( -/- ) knockout males, exhibit coat defects similar to those observed in homozygous olt/olt mutant mice but the spermiogenesis in male offspring is normal. We conclude that the 234-kbp deletion from chromosome 9 harbors a gene involved in spermiogenesis and we propose that the oligotriche mutant be used as a model for the study of the putative tumor suppressor genes Dlec1, Ctdspl, and Vill. We also suggest that the oligotriche locus be named Del(9Ctdspl-Slc22a14)1Pas.

Engrailed-2 regulates genes related to vesicle formation and transport in cerebellar Purkinje cells.

Engrailed transcription factors regulate survival, cell fate decisions and axon pathfinding in central neurons. En-2 can also attenuate Purkinje cell (PC) maturation. Here, we use array analysis to scrutinize gene expression in developing PCs overexpressing Engrailed-2 (L7En-2). The majority (70%) of regulated genes was found down-regulated in L7En-2 cerebella, consistent with the known repressive function of Engrailed-2. Differential gene expression, verified by in situ hybridization or Western blotting, was particularly evident during the first postnatal week, when L7En-2 PCs display conspicuous deficits in dendritogenesis. Functional classification revealed clusters of genes linked to vesicle formation and transport. Consistently, Golgi stacks located at the axonal pole of wild type PC somata were rarely detected in L7En-2 PCs. In addition, long continuous stretches of endoplasmic reticulum typically found around the axonal pole of wild type PCs were less frequently observed in transgenic cells. Engrailed-2 might therefore orchestrate PC survival and process formation as a regulator of subcellular organization.

The bridge-partitioning complex is absent in a distinct type of defective germ cell division in the gonads of the golden hamster.

Intercellular bridges (IBs) connecting the cytoplasms of a defined type of defective germ cell division ("arrested mitoses") in male and female gonads of the immature golden hamster were studied by electron microscopy. In both sexes, such cells appear at the time when germ cells switch from mitotic proliferation to the onset of meiotic prophase, i.e., during a short perinatal period in the female and during pubertal maturation in the male golden hamster. These cells are arrested and finally degenerate. IBs of these cells completely lack the bridge-partitioning complex (BPC), a structure composed of a stack of transverse endomembrane cisternae which normally fills the IBs during subsequent divisions of bridge-connected germ cells. This unique exception from the usual course of clonal proliferation of mammalian germ cells has several implications: (1) The supposed barrier function of the BPC is missing in the defective germ cell divisions; (2) the failure to form the BPC might be related to a disturbed microtubule apparatus in the cells; (3) the absence of the BPC possibly reflects the influence of conflicting environmental signals, inducing both mitotic and early meiotic mechanisms in the cells at this crucial point of gametogenesis.