Biomedical subjects

D Zhang

Publications and source records attributed to D Zhang.

At least 415 records · Page 23Linked to original sources

PubMed1997

Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that binds and activates ErbB4.

We describe the identification of Neuregulin-3 (NRG3), a novel protein that is structurally related to the neuregulins (NRG1). The NRG1/neuregulins are a diverse family of proteins that arise by alternative splicing from a single gene. These proteins play an important role in controlling the growth and differentiation of glial, epithelial, and muscle cells. The biological effects of NRG1 are mediated by receptor tyrosine kinases ErbB2, ErbB3, and ErbB4. However, genetic studies have suggested that the activity of ErbB4 may also be regulated in the central nervous system by a ligand distinct from NRG1. NRG3 is predicted to contain an extracellular domain with an epidermal growth factor (EGF) motif, a transmembrane domain, and a large cytoplasmic domain. We show that the EGF-like domain of NRG3 binds to the extracellular domain of ErbB4 in vitro. Moreover, NRG3 binds to ErbB4 expressed on cells and stimulates tyrosine phosphorylation of this receptor. The expression of NRG3 is highly restricted to the developing and adult nervous system. These data suggest that NRG3 is a novel, neural-enriched ligand for ErbB4.

Amino Acid Sequence↗

PubMed1997

Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis.

Niemann-Pick type C (NP-C) disease, a fatal neurovisceral disorder, is characterized by lysosomal accumulation of low density lipoprotein (LDL)-derived cholesterol. By positional cloning methods, a gene (NPC1) with insertion, deletion, and missense mutations has been identified in NP-C patients. Transfection of NP-C fibroblasts with wild-type NPC1 cDNA resulted in correction of their excessive lysosomal storage of LDL cholesterol, thereby defining the critical role of NPC1 in regulation of intracellular cholesterol trafficking. The 1278-amino acid NPC1 protein has sequence similarity to the morphogen receptor PATCHED and the putative sterol-sensing regions of SREBP cleavage-activating protein (SCAP) and 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase.

Amino Acid Sequence↗

PubMed1997

Substantial narrowing of the Niemann-Pick C candidate interval by yeast artificial chromosome complementation.

Niemann-Pick disease type C (NP-C) is an autosomal recessive lipidosis linked to chromosome 18q11-12, characterized by lysosomal accumulation of unesterified cholesterol and delayed induction of cholesterol-mediated homeostatic responses. This cellular phenotype is identifiable cytologically by filipin staining and biochemically by measurement of low-density lipoprotein-derived cholesterol esterification. The mutant Chinese hamster ovary cell line (CT60), which displays the NP-C cellular phenotype, was used as the recipient for a complementation assay after somatic cell fusions with normal and NP-C murine cells suggested that this Chinese hamster ovary cell line carries an alteration(s) in the hamster homolog(s) of NP-C. To narrow rapidly the candidate interval for NP-C, three overlapping yeast artificial chromosomes (YACs) spanning the 1 centimorgan human NP-C interval were introduced stably into CT60 cells and analyzed for correction of the cellular phenotype. Only YAC 911D5 complemented the NP-C phenotype, as evidenced by cytological and biochemical analyses, whereas no complementation was obtained from the other two YACs within the interval or from a YAC derived from chromosome 7. Fluorescent in situ hybridization indicated that YAC 911D5 was integrated at a single site per CT60 genome. These data substantially narrow the NP-C critical interval and should greatly simplify the identification of the gene responsible in mouse and man. This is the first demonstration of YAC complementation as a valuable adjunct strategy for positional cloning of a human gene.

Animals↗

PubMed1997

2-Oxo-3-alkynoic acids, universal mechanism-based inactivators of thiamin diphosphate-dependent decarboxylases: synthesis and evidence for potent inactivation of the pyruvate dehydrogenase multienzyme complex.

A new class of compounds, the 2-oxo-3-alkynoic acids with a phenyl substituent at carbon 4 was reported by the authors as potent irreversible and mechanism-based inhibitors of the thiamin diphosphate- (ThDP-) dependent enzyme pyruvate decarboxylase [Chiu, C.-F., & Jordan, F. (1994) J. Org. Chem. 59, 5763-5766]. The method has been successfully extended to the synthesis of the 4-, 5-, and 7-carbon aliphatic members of this family of compounds. These three compounds were then tested on three ThDP-dependent pyruvate decarboxylases: the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc) and its E1 (ThDP-dependent) component, pyruvate oxidase (POX, phosphorylating; from Lactobacillus plantarum),and pyruvate decarboxylase (PDC) from Saccharomycescerevisiae. All three enzymes were irreversibly inhibited by the new compounds. The 4-carbon acid is the best substrate-analog inactivator known to date for PDHc, more potent than either fluoropyruvate or bromopyruvate. The following conclusions were drawn from extensive studies with PDHc: (a) The kinetics of inactivation of PDH complexes and of resolved E1 by 2-oxo-3-alkynoic acids is time- and concentration-dependent. (b) The 4-carbon acid has a Ki 2 orders of magnitude stronger than the 5-carbon acid, clearly demonstrating the substrate specificity of PDHc. (c) The rate of inactivation of PDH complexes and of resolved E1 by 2-oxo-3-alkynoic acids is enhanced by the addition of ThDP and MgCl2. (d) Pyruvate completely protects E1 and partially protects PDHc from inactivation by 2-oxo-3-butynoic acid. (e) E1 but not E2-E3 is the target of inactivation by 2-oxo-3-butynoic acid. (f) Inactivation of E1 by 2-oxo-3-butynoic acid is accompanied by modification of 1.3 cysteines/E1 monomer. The order of reactivity with the 4-carbon acid was PDHc > POX > PDC. While the order of reactivity with PDHc and POX was 2-oxo-3-butynoic acid > 2-oxo-3-pentynoic acid > 2-oxo-3-heptynoic acid, the order of reactivity was reversed with PDC.

Bacterial Proteins↗

PubMed1997

Fractal Dimensions of Coals and Cokes

Using adsorption data, we get formulas for the calculation of fractal dimensions: log[A CO2 (DP) /A N2 (BET) ] = -5.3984(2 - D 1 )/2 and log[A CO2 (BET) /A N2 (BET) ] = -4.9569(2 - D 2 )/2. The fractal dimensions (D ) of 27 coals and 2 cokes have been obtained. The D of coals decreased with the increase of fa and reached a maximum at H/C equal to 0.66 (or C daf about 86%). The fractal dimension is relative to ash and volatiles of coal: D = 2.2237 + 0.6249V daf + 0.8863A d . The relationship between D of coal coke and its conversions (X ) obeys the following equation: D = a exp(-bX ) + c .

Journal Article↗

PubMed1997

Vitamin E inhibits apoptosis, DNA modification, and cancer incidence induced by iron-mediated peroxidation in Wistar rat kidney.

We have developed an experimental model of iron-induced oxidative nephrotoxicity and renal cancer. Using this model, the effect of vitamin E, a known antioxidant, was investigated. Three-week-old male Wistar rats were fed with vitamin E-sufficient (control) and vitamin E-supplemented diets throughout the experiment. After 1 month of feeding, iron-induced tissue lipid peroxidation, apoptosis, and formation of 8-hydroxydeoxyguanosine, a known DNA oxidative modification, were observed by cold Schiff staining, in situ labeling method (staining by terminal deoxynucleotidyl transferase-mediated nick end labeling), and high-performance liquid chromatography with electrochemical detection system, respectively, in the groups of rats treated with ferric nitrilotriacetate (Fe-NTA; Fe, 10 mg/kg body weight). For the vitamin E intervention study on Fe-NTA-induced renal carcinogenesis, two groups of rats fed vitamin E-sufficient and vitamin E-supplemented diets (30 and 20 rats, respectively) were treated with Fe-NTA (Fe, 7.5 mg/kg body weight once or twice a week) i.p. for 3 months and observed for 9 additional months. Five of the vitamin E-sufficient rats died during the first 3-month period. The results showed that vitamin E could inhibit tissue lipid peroxidation, apoptosis, 8-hydroxydeoxyguanosine formation, and the development of cancer [11 of 25 rats (44%) for vitamin E-sufficient versus 1 of 20 rats (5%) for vitamin E-supplemented rats, respectively]. These studies strongly suggest that in Fe-NTA-induced renal cancer, as with certain other types of cancer, oxidative stress plays an important role in carcinogenesis, and an antioxidant is an effective chemopreventive measure.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1997

Agonist-induced closure of constitutively open gamma-aminobutyric acid channels with mutated M2 domains.

Ligand-gated ion channels display a fundamental property-channels remain virtually closed at rest and open upon agonist binding. Here we show that substituting alanines for either of two amino acid residues (T314 or L317) in the M2 region of the gamma-aminobutyric acid (GABA) rho1 subunit results in spontaneous channel opening in the absence of ligand. Surprisingly, for two single point mutants (T314A or L317A), application of very low concentrations of agonist partially suppressed this spontaneous current, while higher concentrations re-activated the receptors. When both of these sites were mutated (T314A/L317A), GABA nearly completely suppressed the constitutive current and did not re-activate the current even at very high concentrations. This study provides important new insights into the structure-function relationship of ligand-gated ion channels, where modification of the structure of the channel pore region not only alters the allosteric transition of the receptor protein but also reverses the polarity of agonist regulation of channel gating. Our results suggest that the sites where these two residues are located are structurally critical for channel gating.

Amino Acid Sequence↗

PubMed1997

The multiple inhibitory mechanisms of GEM 91, a gag antisense phosphorothioate oligonucleotide, for human immunodeficiency virus type 1.

GEM 91 (gene expression modulator) is a 25-mer oligonucleotide phosphorothioate complementary to the gag initiation site of HIV-1. GEM 91 has been studied in various in vitro cell culture models to examine inhibitory effects on different stages of HIV-1 replication. Experiments were focused on the binding of virions to the cell surface, inhibition of virus entry, reverse transcription (HIV DNA production), inhibition of steady state viral mRNA levels, inhibition of virus production from chronically infected cells, and inhibition of HIV genome packaging within virions. Experiments were also performed in vitro in an attempt to generate strains of HIV with reduced sensitivity to GEM 91. We observed sequence-dependent inhibition of virus entry/reverse transcription and a reduction in steady state viral RNA levels. We also observed sequence-independent inhibition of virion binding to cells and inhibition of virus production by chronically infected cells. Using in vitro methods that were successful in generating HIV strains with reduced sensitivity to AZT, we were unable to generate strains with reduced sensitivity to GEM 91.

Anti-HIV Agents↗

PubMed1997

Prevalence and predictive value of p53 mutation in patients with oesophageal squamous cell carcinomas: a prospective clinico-pathological study and survival analysis of 70 patients.

The tissues from 70 Chinese patients with oesophageal squamous cell carcinoma were prospectively collected to study for the pattern of p53 mutations and its relationship with clinico-pathological features and prognosis using immunohistochemistry, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing. p53 over-expression and p53 mutations were detected in 73% and 44% of the patients. These p53 aberrations had no relationship with the patient age, sex, smoking/drinking habits and tumor site, size or stage. The p53 over-expression was more intense in moderately/poorly-differentiated squamous cell carcinomas. Thirty-three p53 mutations were noted in 31 patients; 18.2% in exon 5, 15.2% in exon 6, 33.3% in exon 7 and 33.3% in exon 8. Mutations were primarily point mutations and common in codons 248, 273 and 285. There were 46% transversions, 36% transitions and 18% frameshift. The survival of the patients depended mainly on the extent of resection. In patients with stage III oesophageal cancer, the median survival of those with p53 mutations was 6.8 months whereas those without was 12.5 months. The results were of clinical importance although the value did not reach statistical significance. Thus, there was a definite role of p53 mutations in the pathogenesis of oesophageal squamous cell carcinomas. p53 mutations were not synonymous with p53 over-expression. The distribution of p53 mutations in oesophageal cancers suggested that the etiologic contribution might be complex and probably involve different exogenous and endogenous exposures. p53 mutations also appear to play a role in predicting the survival of patients with stage III oesophageal squamous cell carcinomas.

Adult↗

PubMed1997

Molecular cloning and comparative analysis of the rhesus macaque costimulatory molecules CD80 (B7-1) and CD86 (B7-2).

To facilitate analysis of the role of costimulatory molecules in a nonhuman primate model, we cloned and sequenced the CD80 (B7-1) and CD86 (B7-2) costimulatory molecules from rhesus macaques. Rhesus CD80 and CD86 were highly homologous to their human counterparts, with overall amino acid homologies of greater than 90%, and were specifically recognized by murine antihuman CD80 or CD86 monoclonal antibodies. Stable cell lines expressing rhesus CD80 or CD86 induced proliferation of suboptimally activated CD4+ T cells and transcription of cytokine mRNA. Both CD80 and CD86 were able to provide costimulation for interferon-gamma and IL-2 synthesis by rhesus CD4+ T cells, but CD80 costimulation also resulted in synthesis of IL-4 and IL-10. The high degree of homology between the rhesus and the human CD80 and CD86 molecules should facilitate analysis of therapeutic interventions directed at this costimulatory pathway in nonhuman primates.

Amino Acid Sequence↗

PubMed1997

Molecular cloning and characterization of a novel human receptor protein tyrosine phosphatase gene, hPTP-J: down-regulation of gene expression by PMA and calcium ionophore in Jurkat T lymphoma cells.

A novel cDNA encoding a 1436 aa protein was cloned using a PCR system with degenerate primers. This new gene, hPTP-J, was found to encode a PTP protein consisting of an extracellular region containing an MAM (meprin, A5, mu)-like domain, an immunoglobulin-like domain, four fibronectin type-III repeats, a transmembrane region, and a cytoplasmic region containing two tandemly repeated PTP domains hPTP-J is thus considered to be a new member of the type II receptor PTP (RPTP) subfamily, like RPTP mu and RPTP kappa. hPTP-J gene expression was strongly detected in skeletal muscle and moderately detected in the prostate, pancreas, placenta, and heart, but was only weakly detected in the peripheral blood lymphocytes, thymus, and spleen even though gene expression was relatively high in the Jurkat T lymphoma cell line. Moreover, hPTP-J gene expression was down-regulated after Jurkat cells were stimulated by either PMA or calcium ionophore. Based on these findings, it is suggested that some signaling pathways mediated by PMA and/or intracellular calcium are involved in the regulation of hPTP-J gene expression in Jurkat cells.

Amino Acid Sequence↗

PubMed1997

The role of temporal sensing in bioelectromagnetic effects.

Experiments were conducted to see whether the cellular response to electromagnetic (EM) fields occurs through a detection process involving temporal sensing. L929 cells were exposed to 60 Hz magnetic fields and the enhancement of ornithine decarboxylase (ODC) activity was measured to determine cellular response to the field. In one set of experiments, the field was turned alternately off and on at intervals of 0.1 to 50 s. For these experiments, field coherence was maintained by eliminating the insertion of random time intervals upon switching. Intervals < or = 1 s produced no enhancement of ODC activity, but fields switched at intervals > or 10 s showed ODC activities that were enhanced by a factor of approximately 1.7. These data indicate that it is the interval over which field parameters (e.g., amplitude or frequency) remain constant, rather than the interval over which the field is coherent, that is critical to cellular response to an EMF. In a second set of experiments, designed to determine how long it would take for cells to detect a change in field parameters, the field was interrupted for brief intervals (25-200 ms) once each second throughout exposure. In this situation, the extent of EMF-induced ODC activity depended upon the duration of the interruption. Interruptions > or = 100 ms were detected by the cell as shown by elimination of field-induced enhancement of ODC. That two time constants (0.1 and 10 s) are involved in cellular EMF detection is consistent with the temporal sensing process associated with bacterial chemotaxis. By analogy with bacterial temporal sensing, cells would continuously sample and average an EM field over intervals of about 0.1 s (the "averaging" time), storing the averaged value in memory. The cell would compare the stored value with the current average, and respond to the EM field only when field parameters remain constant over intervals of approximately 10 s (the "memory" time).

Animals↗

PubMed1997

Molecular and functional analysis of the ribosomal L11 and S12 protein genes (rplK and rpsL) of Streptomyces coelicolor A3(2).

A RelC deletion mutant, KO-100, of Streptomyces coelicolor A3(2) has been isolated from a collection of spontaneous thiostrepton-resistant mutants. KO-100 grows as vigorously as the parent strain and possesses a 6-bp deletion within the rplK, previously termed relC. When the wild-type rplK gene was propagated on a low-copy-number vector in mutant KO-100, the ability to produce ppGpp, actinorhodin and undecylprodigiosin, which had been lost in the RelC mutant, was completely restored. Allele replacement by gene homogenotization demonstrated that the RelC mutation is responsible for the resistance to thiostrepton and the inactivation of ppGpp, actinorhodin and undecylprodigiosin production. Western blotting showed that ribosomes from the RelC mutant KO-100 contain only one-eighth the amount of L11 protein found in ribosomes of the parent strain. The impairment of antibiotic production in KO-100 could be rescued by the introduction of mutations that confer resistance to streptomycin (str), which result in alteration of Lys-88 in ribosomal protein S12 to Glu or Arg. No accompanying restoration of ppGpp synthesis was detected in these RelC str double mutants.

Alleles↗

PubMed1997

Molecular analysis of the ribosomal L11 protein gene (rplK = relC) of Streptomyces griseus and identification of a deletion allele.

The rplK (= relC) gene, which codes for ribosomal protein L11, was cloned from Streptomyces griseus IFO13189 using a screening procedure based on polymerase chain reaction amplification of a gene segment that subsequently allowed the isolation of the complete gene from a gene library. rplK lies between the nusG gene, encoding a protein involved in antitermination of transcription, and the rplA gene, which encodes the ribosomal protein L1. Comparison of the rplK gene sequences of the wild-type strain and the presumed relC mutant strain 3-3 (originally isolated as a thiopeptin-resistant isolate) revealed a 12-bp deletion within the rplK gene from the mutant, flanked by a 4-bp repeat sequence in the corresponding region in the wild type. When the wild-type rplK gene was propagated on a low-copy-number vector in the relC mutant 3-3, the ability to produce guanosine 5'-diphosphate 3'-diphosphate, streptomycin, and submerged spores was completely restored to parental levels. The impaired ability to form aerial mycelium was, however, unaffected. Western blotting analysis showed that the ribosomes from the relC mutant 3-3 incorporate the mutant L11 protein normally, although the level of incorporation is approximately one-third that of the wild-type L11 protein in ribosomes of the parent strain. Propagation of the mutant rplK gene in the wild-type strain resulted in marked defects in growth, streptomycin production, and aerial mycelium formation, indicating that the mutant L11 protein exerts certain negative effects in the cells.

Alleles↗

PubMed1997

Effects of Microplitis croceipes Teratocytes on Host Haemolymph Protein Content and Fat Body Proliferation.

Qualitative and quantitative changes in haemolymph proteins in Heliothis virescens were observed in larvae injected with either Microplitis croceipes teratocytes or teratocyte secreted proteins (TSP). Haemolymph protein titres in hosts receiving either 0.5 or 1 larval equivalent (LE) of teratocytes were similar to those of parasitized larvae, whereas a single injection of 4LE of TSP was required to induce a similar response. SDS-PAGE showed that the 82kDa monomer of riboflavin-binding protein and the 74/76kDa monomers of storage proteins were significantly reduced in parasitized larvae and in nonparasitized larvae treated with TSP. Concentrations of a 155kDa monomer (insectacyanin chromoprotein) also were reduced in parasitized larvae and those injected with either teratocytes or TSP. Two monomers (56 and 60kDa) were unique to parasitized larvae. Treated larvae required several days longer than controls to reach a comparable premetamorphic stage (burrowing-digging). Reductions in fat body proliferation similar to those seen in parasitized larvae were observed in larvae treated with either 1LE of teratocytes, or with 2 or 4LEs of TSP. Perivisceral fat body weights from larvae treated with either 0.25 or 0.5LE of teratocytes were significantly reduced, but less so than those which received 1LE. Thus, fat body proliferation in both teratocyte- and TSP-treated larvae was inhibited in a dose-dependent manner. Both light- and transmission electron microscopy observations revealed cytological differences in fat body tissues of larvae injected with either teratocytes or TSP from the condition observed in parasitized larvae and noninjected controls. Gross dissection of periviseral fat body from parasitized, teratocyte-injected and TSP-injected larvae showed tissue much less developed and differing considerably in appearance from controls. Observed differences included reduced size and/or number of lipid bodies and qualitative and quantitative changes in other cytoplasmic organelles.

Journal Article↗

PubMed1997

Oligosaccharide polyesters from roots of Polygala fallax.

Five new oligosaccharide polyesters, fallaxoses A-E, along with four known ones, reiniose D, senegose G, tenuifolioses C and P, were isolated from the roots of Polygala fallax. Fallaxoses A-E were elucidated as 3-O-{4-O-[beta-D-glucopyranosyl-(1-->4)- alpha-L-rhamnopyranosyl]-feruloyl}-beta-D-fructofuranosyl- (2-->1)-(4,6-di-O-benzoyl)-alpha-D-glucopyranoside, 3-O-{4-O-[beta-D-glucocopyranosyl-(1-->3)-(2-O-acetyl)- alpha-L-rhamnopyranosyl]-feruloyl}-beta-D-fructofuranosyl-(2-->1)- (4, 6-di-O-benzoyl)-alpha-D-glucopyranoside, 1-O-p-coumaroyl-(3-O-benzoyl)-beta-D-fructofuranosyl-(2-->1)- [beta-D-glucopyranosyl-(1-->2)]-[6-O-acetyl-beta-D-glucopyranosyl- (1-->3)]-(4-O-p-coumaroyl)-alpha-D-glucopyranoside, 1-O-p-coumaroyl-(3-O-benzoyl)-beta-D-fructofuranosyl-(2-->1)- [beta-D-glucopyranosyl-(1-->2)]-[6-O-acetyl-beta-D-glucopyranosyl-(1-->3 )]-(4-O-feruloyl)-alpha-D-glucopyranoside, 1-O-feruloyl-(3-O-benzoyl)-beta-D-fructofuranosyl-(2-->1)- [beta-D-glucopyranosyl-(1-->2)]-[beta-D-glucopyranosyl- (1-->3)-(6-O-acetyl)-beta-D-glucopyranosyl-(1-->3)]- (6-O-feruloyl)-alpha-D-glucopyranoside, respectively, by spectroscopic and chemical means.

Carbohydrate Conformation↗

PubMed1997

Presence of human papillomavirus in esophageal squamous cell carcinomas of Hong Kong Chinese and its relationship with p53 gene mutation.

There is no scientific study that has investigated the association between human papilloma virus (HPV) and p53 mutation in Hong Kong Chinese patients with esophageal cancers. The aim of this survey is to evaluate in details the prevalence and relationship of HPV and p53 mutation in these patients with esophageal squamous cell carcinomas. Fresh tissues from the resected specimens of 70 Chinese patients (59 men, 11 women) with primary esophageal squamous cell carcinomas (20 well-differentiated, 36 moderately differentiated, and 14 poorly differentiated squamous cell carcinomas) were tested for the presence of HPV and p53 mutation using the polymerase chain reaction (PCR), single-strand conformational polymorphism (SSCP) analysis, and DNA sequencing. No HPV type 18 was detected, whereas HPV type 16 was identified in 8.6% (6 of 75) of the cases. p53 mutation was found in 44% (31 of 70) of the tumors. The mean ages of HPV-positive and HPV-negative groups of patients were 55 and 64 years, respectively (P = .046, t-test). There was no correlation between the prevalence of HPV and p53 mutation in these tumors. The presence of HPV and p53 also had no relation to the sex of the patients or to the grade of the carcinomas. It is concluded that the overall low prevalence of HPV in esophageal carcinomas may suggest that the virus may not play an important role in the pathogenesis of these tumors in Hong Kong Chinese patients. Also, p53 mutation and integrated HPV DNA are not mutually exclusive in esophageal cancer.

Adult↗

PubMed1997

Bone morphogenetic proteins in the nervous system.

Bone morphogenetic proteins (BMPs) are a rapidly expanding subclass of the transforming growth factor superfamily. BMP ligands and receptor subunits are present throughout neural development within discrete regions of the embryonic brain and within neural crest-derived pre- and post-migratory zones. BMPs initially inhibit the formation of neuroectoderm during gastrulation while, within the neural tube, they act as gradient morphogens to promote the differentiation of dorsal cell types and intermediate cell types throughout co-operative signaling. In the peripheral nervous system, BMPs act as instructive signals for neuronal lineage commitment and promote graded stages of neuronal differentiation. By contrast, within the CNS, these same factors promote astroglial lineage elaboration from embryonic subventricular zone progenitor cells, with concurrent suppression of the neuronal or oligodendroglial lineages, or both. In addition, BMPs act on more lineage-restricted embryonic CNS progenitor cells to promote regional neuronal survival and cellular differentiation. Furthermore, these versatile cytokines induce selective apoptosis of discrete rhombencephalic neural crest-associated cellular populations. These observations suggest that the BMPs exhibit a broad range of cellular and context-specific effects during multiple stages of neural development.

Animals↗