Asymmetric localization and function of cell-fate determinants: a fly's view

One mechanism to generate daughter cells with distinct fates is the asymmetric inheritance of regulatory proteins, leading to differential gene regulation in the daughter cells. This mode of cell division is termed 'asymmetric cell division.' The nervous system of the fly employs asymmetric cell division, both in the central nervous system, to generate neural precursors, neurons and glial cells; and in the peripheral nervous system, to create sensory organs that are composed of multiple cell types. These cell lineages are excellent models to examine the gene expression program that leads to fate acquisition, the cell-fate determinants that control these programs and how these determinants, in turn, are distributed through cell polarity machinery.     

Multiple roles of mouse Numb in tuning developmental cell fates.

BACKGROUND: Notch signaling regulates multiple differentiation processes and cell fate decisions during both invertebrate and vertebrate development. Numb encodes an intracellular protein that was shown in Drosophila to antagonize Notch signaling at binary cell fate decisions of certain cell lineages. Although overexpression experiments suggested that Numb might also antagonize some Notch activity in vertebrates, the developmental processes in which Numb is involved remained elusive. RESULTS: We generated mice with a homozygous inactivation of Numb. These mice died before embryonic day E11.5, probably because of defects in angiogenic remodeling and placental dysfunction. Mutant embryos had an open anterior neural tube and impaired neuronal differentiation within the developing cranial central nervous system (CNS). In the developing spinal cord, the number of differentiated motoneurons was reduced. Within the peripheral nervous system (PNS), ganglia of cranial sensory neurons were formed. Trunk neural crest cells migrated and differentiated into sympathetic neurons. In contrast, a selective differentiation anomaly was observed in dorsal root ganglia, where neural crest--derived progenitor cells had migrated normally to form ganglionic structures, but failed to differentiate into sensory neurons. CONCLUSIONS: Mouse Numb is involved in multiple developmental processes and required for cell fate tuning in a variety of lineages. In the nervous system, Numb is required for the generation of a large subset of neuronal lineages. The restricted requirement of Numb during neural development in the mouse suggests that in some neuronal lineages, Notch signaling may be regulated independently of Numb.     

脑细胞增殖研究进展

本文综述了脑细胞增殖发生的主要区域和命运、影响脑细胞增殖的主要因素及脑细胞增殖在干细胞治疗中的应用前景与存在的问题等.     

Small temporal RNAs in animal development

The lin-4/miR-125 and let-7 microRNAs are at the heart of the heterochronic pathway, which controls temporal cell fate determination during Caenorhabditis elegans development. These small temporal RNAs are clustered along with a third microRNA, miR-100, in the genomes of most animals. Their conserved temporal and neural expression profile suggests a general role in cell fate determination during nervous system differentiation. By triggering consecutive differentiation programs, these microRNAs probably help to determine birth-order dependent temporal identity and thereby contribute to neural stem cell multipotency.     

Smad10 is required for formation of the frog nervous system

Before the nervous system establishes its complex array of cell types and connections, multipotent cells are instructed to adopt a neural fate and an anterior-posterior pattern is established. In this report, we show that Smad10, a member of the Smad family of intracellular transducers of TGFbeta signaling, is required for formation of the nervous system. In addition, two types of molecules proposed as key to neural induction and patterning, bone morphogenetic protein (BMP) antagonists and fibroblast growth factor (FGF), require Smad10 for these activities. These data suggest that Smad10 may be a central mediator of the development of the frog nervous system.     

Isolation of a murine homologue of the Drosophila neuralized gene, a gene required for axonemal integrity in spermatozoa and terminal maturation of the mammary gland

The Drosophila neuralized gene shows genetic interactions with Notch, Enhancer of split, and other neurogenic genes and is thought to be involved in cell fate specification in the central nervous system and the mesoderm. In addition, a human homologue of the Drosophila neuralized gene has been described as a potential tumor suppressor gene in malignant astrocytomas. We have isolated a murine homologue of the Drosophila and human Neuralized genes and, in an effort to understand its physiological function, derived mice with a targeted deletion of this gene. Surprisingly, mice homozygous for the introduced mutation do not show aberrant cell fate specifications in the central nervous system or in the developing mesoderm. This is in contrast to mice with targeted deletions in other vertebrate homologues of neurogenic genes such as Notch, Delta, and Cbf-1. Male Neuralized null mice, however, are sterile due to a defect in axoneme organization in the spermatozoa that leads to highly compromised tail movement and sperm immotility. In addition, female Neuralized null animals are defective in the final stages of mammary gland maturation during pregnancy.     

Apoptotic and Non-apoptotic Caspase Functions in Neural Development

During neural development, massive cell death occurs in both vertebrates and invertebrates. Caspase is a central player in apoptosis that is evolutionally conserved. Genetic manipulation of the caspase activity in Drosophila and mice has revealed that caspases control cell fate through apoptotic and non-apoptotic mechanisms, to ensure appropriate cell differentiation and maturation in the developing nervous system.     

神经干细胞移植的临床研究进展

神经系统损伤会导致脑内神经干细胞（neural stem cells,NSCs）的扩增以实现自我修复功能,而通过外源细胞移植的方式来加速这一进程,可能是一种更有效的治疗手段。当前,神经干细胞临床研究所面临的主要问题是如何评价细胞在移植后的行为和功能。该文综述了近几年使用神经干细胞移植治疗几种主要神经系统疾病的临床研究成果,并着重关注了干细胞移植后的示踪研究。