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Ganglioside GM3: an acidic membrane component that increases during macrophage-like cell differentiation can induce monocytic differentiation of human myeloid and monocytoid leukemic cell lines HL-60 and U937.

When human myeloid and monocytoid leukemic cell lines HL-60 and U937, respectively, were treated with an exogenous sialoglycosphingolipid, ganglioside GM3, in serum-free medium, cell growth was markedly inhibited, and their morphological maturation along a monocytic lineage was observed. In addition to a significant increase in phagocytic and nonspecific esterase activities, marked increase of monocyte-specific surface antigens detectable with monoclonal antibodies such as OKM1 and OKM5 was observed in GM3-fed cells. Other sialoglycosphingolipids with the carbohydrate structure belonging to ganglio-series oligosaccharide, ganglioside GM1 and a brain ganglioside mixture, had no effect on the cell differentiation, showing instead stimulatory actions on the growth of these cell lines. We recently demonstrated that the ganglio-series ganglioside GM3 characteristically increased during macrophage-like cell differentiation of these cell lines. The present results indicate that ganglioside molecular species that specifically increase during monocytic cell differentiation of human myeloid and monocytoid leukemic cell lines may play, in turn, an important role in the differentiation-induction of these cell lines along a monocytic cell lineage.

Animals↗

Differential recognition of histone H10 by monoclonal antibodies during cell differentiation and the arrest of cell proliferation.

Individual anti-H1(0) monoclonal antibodies were screened in an immunolocalization assay to isolate clones able to recognize H1(0) in a differentiation-dependent manner using a murine erythroleukemia cell line. Two clones were selected, one recognizing H1(0) only in differentiating cells (clone 27 antibody), and the other recognizing the protein constitutively (clone 34 antibody). Both antibodies recognized a restricted region of the protein located at the N-terminal part of the globular domain. Amino acids 24-30, essential for the recognition of the protein by the clone 27 antibody, are extremely conserved in all known H1(0)-like proteins from sea urchin to human. Within these residues, proline 26, responsible for a bend in this region, plays a particularly important role in the epitope recognition. The region involved in the protein recognition by clone 34 antibody is larger and encompasses amino acids 20-30. However, proline 26 does not play an essential role in the structure of this epitope. Detailed analysis of the differential recognition of H1(0) in chromatin during cell differentiation and proliferation suggests that the modification of chromatin structure as well as that of H1(0) conformation can account for this effect. Indeed, in vitro study of H1(0)-four-way junction DNA interaction showed that the N-terminal tail domain of the protein can influence the recognition of H1(0) by these antibodies when the protein interacts with DNA. The two monoclonal antibodies described here therefore seem to be valuable tools for investigating fine modulations in chromatin structure and the concomitant changes occurring in the conformation of the protein.

Amino Acid Sequence↗

Differential coupling of alpha1-, alpha2-, and beta-adrenergic receptors to mitogen-activated protein kinase pathways and differentiation in transfected PC12 cells.

Three adrenergic receptor families that selectively activate three different G proteins (alpha1/Gq/11, alpha2/Gi, and beta/Gs) were used to study mitogen-activated protein kinase (MAPK) activation and differentiation in PC12 cells. PC12 cells were stably transfected with alpha1A-, alpha2A-, or beta1-adrenergic receptors (ARs) in an inducible expression vector, and subclones were characterized. Norepinephrine stimulated inositol phosphate formation in alpha1A-transfected cells, inhibited cyclic adenosine 3'5'-monophosphate (cAMP) formation in alpha2A-transfected cells, and stimulated cAMP formation in beta1-transfected cells. Nerve growth factor activated extracellular signal-regulated kinases (ERKs) in all cell lines; however, norepinephrine activated ERKs only in alpha1A- and beta1-transfected cells but not in alpha2A-transfected cells. Norepinephrine also activated c-Jun NH2-terminal kinase and p38 MAPK in alpha1A-transfected cells but not in beta1- or alpha2A-transfected cells. Norepinephrine caused differentiation of PC12 cells expressing alpha1A-ARs but not those expressing beta1- or alpha2A-ARs. However, norepinephrine acted synergistically with nerve growth factor in promoting differentiation of cells expressing beta1-ARs. Whereas ERKs are activated by Gi- but not Gs-linked receptors in many fibroblastic cell lines, we observed the opposite in PC12 cells. The results show that activation of the different G protein signaling pathways has different effects on MAPKs and differentiation in PC12 cells, with Gq signaling pathways activating all three major MAPK pathways.

Adrenergic alpha-Agonists↗

Transcriptional control of the pref-1 gene in 3T3-L1 adipocyte differentiation. Sequence requirement for differentiation-dependent suppression.

Preadipocyte factor-1 (Pref-1) is a transmembrane epidermal growth factor-like domain-containing protein highly expressed in 3T3-L1 preadipocytes, but is undetectable in mature fat cells; this down-regulation is required for adipocyte differentiation. We show here that pref-1 transcription is markedly suppressed during adipose conversion and results in decreased Pref-1 RNA levels. Using 3T3-L1 cells stably transfected with Pref-1 5'-deletion constructs truncated at -6000, -2100, -1300, -692, -300, -235, -193, -183, -170, -93, and -45 base pairs, we determined that the -183 to -170 region is responsible for the suppression of the pref-1 gene during adipogenesis. This is distinct from the -93 to -45 sequence important for pref-1 promoter activity in preadipocytes. The placement of a 40-base pair -193 to -154 pref-1 sequence containing the putative SAD (suppression in adipocyte differentiation) element upstream of the SV40 promoter decreased promoter activity by 85% upon adipocyte differentiation, compared with 40% observed with the SV40 promoter alone. The SAD element is therefore sufficient for adipocyte differentiation-dependent down-regulation of a heterologous promoter. A DNA-protein complex was observed when the -193 to -174 sequence was used with 3T3-L1 nuclear extracts in gel mobility shift assays. Competition with oligonucleotides harboring base substitution mutations identified a core sequence of -183AAAGA-179 as crucial for DNA-protein complex formation. UV cross-linking predicts that an approximately 63-kDa protein specifically binds the SAD element.

3T3 Cells↗

CSX/Nkx2.5 modulates differentiation of skeletal myoblasts and promotes differentiation into neuronal cells in vitro.

CSX/Nkx2.5 transcription factor plays a pivotal role in cardiac development; however, its role in development and differentiation of other organs has not been investigated. In this study, we used C2C12 myoblasts and human fetal primary myoblasts to investigate the function of Nkx2.5 in skeletal myogenesis. The expression levels of Nkx2.5 decreased as C2C12 myoblasts elongated and fused to form myotubes. The expression of human NKX2.5 in C2C12 myoblasts inhibited myocyte differentiation and myotube formation, and up-regulated Gata4 and Tbx5 expression. The expression of NKX2.5 in terminally differentiated C2C12 myotubes resulted in a change in morphology and breakdown into smaller myotubes. Furthermore, overexpression of NKX2.5 in C2C12 cells and primary cultures of human fetal myoblasts led to differentiation of myoblasts into neuron-like cells and expression of neuronal markers. This study sheds light on the previously unknown non-cardiac functions of Nkx2.5 transcription factor.

Adenoviridae↗

Focal parietal cell differentiation in a well-differentiated (intestinal-type) early gastric cancer.

A well-differentiated (intestinal-type) early gastric cancer characterized by multifocal areas containing adenocarcinoma cells with eosinophilic cytoplasm is presented. The electron microscopy revealed that cytoplasmic eosinophilia was mainly due to the presence of numerous mitochondria. In addition, individual cells showed features of preparietal cell differentiation such as numerous mitochondria, tubulovesicles, intracellular canaliculi and rare mucin granules. There were also adenocarcinoma cells with a pyloric gland (mucopeptic) differentiation as revealed by the presence of granules with a dense protein core eccentrically located in the mucus matrix. These ultrastructural data suggested a gastric epithelial cell differentiation. The implications with regard to the classification and histogenesis of this tumor are discussed.

Adenocarcinoma↗

Glucocorticoid effects on the skeletal muscle differentiation program: analysis of clonal proliferation, morphological differentiation and the expression of muscle-specific and regulatory genes.

We examined the effect of glucocorticoids on the proliferation and differentiation of skeletal muscle cells using the C2C12 cell line. We found that treatment with glucocorticoids enhanced muscle cell differentiation but had only minor effects on the clonal growth rate of C2C12 cells. The stimulatory effect of glucocorticoids on myogenic differentiation was reflected in the increased expression of muscle-specific genes, creatine kinase (CK) and acetylcholine receptor gamma subunit (AChR). Dexamethasone had no effect on CK and AChR mRNA stability and enhanced transcription from a CAT reporter genes containing the 3.3kb 5' flanking region of the murine CK gene (-3300MCK-CAT). Since dexamethasone did not affect the expression levels of the myogenic regulatory genes such as myoD and myogenin, the enhancement of muscle-specific transcription might reflect an increase in the functional activity of the regulatory proteins. Other possible mechanisms involved in the differentiation-enhancing effect of glucocorticoids are discussed.

Cell Differentiation↗

Chondrogenic differentiation of clonal mouse embryonic cell line ATDC5 in vitro: differentiation-dependent gene expression of parathyroid hormone (PTH)/PTH-related peptide receptor.

The regulatory role of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) signaling has been implicated in embryonic skeletal development. Here, we studied chondrogenic differentiation of the mouse embryonal carcinoma-derived clonal cell line ATDC5 as a model of chondrogenesis in the early stages of endochondral bone development. ATDC5 cells retain the properties of chondroprogenitor cells, and rapidly proliferate in the presence of 5% FBS. Insulin (10 micrograms/ml) induced chondrogenic differentiation of the cells in a postconfluent phase through a cellular condensation process, resulting in the formation of cartilage nodules, as evidenced by expression of type II collagen and aggrecan genes. We found that differentiated cultures of ATDC5 cells abundantly expressed the high affinity receptor for PTH (Mr approximately 80 kD; Kd = 3.9 nM; 3.2 x 10(5) sites/cell). The receptors on differentiated cells were functionally active, as evidenced by a PTH-dependent activation of adenylate cyclase. Specific binding of PTH to cells markedly increased with the formation of cartilage nodules, while undifferentiated cells failed to show specific binding of PTH. Northern blot analysis indicated that expression of the PTH/PTHrP receptor gene became detectable at the early stage of chondrogenesis of ATDC5 cells, preceding induction of aggrecan gene expression. Expression of the PTH/PTHrP receptor gene was undetectable in undifferentiated cells. The level of PTH/PTHrP receptor mRNA was markedly elevated parallel to that of type II collagen mRNA. These lines of evidence suggest that the expression of functional PTH/PTHrP receptor is associated with the onset of chondrogenesis. In addition, activation of the receptor by exogenous PTH or PTHrP significantly interfered with cellular condensation and the subsequent formation of cartilage nodules, suggesting a novel site of PTHrP action.

Adenylyl Cyclases↗

Lhx9 and lhx9alpha: differential biochemical properties and effects on neuronal differentiation.

The Lhx9 LIM-homeodomain transcription factor and its truncated isoform Lhx9alpha are generated by alternative splicing of the Lhx9 gene. Here we investigated the differential functional properties of these two isoforms. Lhx9alpha, which lacks parts of the homeodomain, was unable to bind DNA in EMSA experiments, but was able to associate with CLIM cofactors in GST pull-down assays. In transfection experiments in PC12 cells, Lhx9alpha fusion constructs systematically showed a nuclear localization, as opposed to Lhx9 fusion constructs, which also localized to the cytoplasm. Moreover, Lhx9 increased NGF-induced neuronal differentiation of PC12 cells. Lhx9alpha, on the other hand, did not significantly increase neuronal differentiation but had an effect on the morphology of PC12 cells. Finally, as tested by RT-PCR experiments on transfected PC12 cells, Lhx9 was not able to induce the transcription of Lhx9alpha. Our results show significantly different functional properties for Lhx9 and Lhx9alpha, and suggest that Lhx9alpha can compete away limiting amounts of nuclear CLIM cofactors. Thus, Lhx9 and Lhx9alpha isoforms could be implicated in regulating various aspects of neuronal differentiation.

Animals↗

Mitochondrial development during life cycle differentiation of African trypanosomes: evidence for a kinetoplast-dependent differentiation control point.

Life cycle differentiation of African trypanosomes entails developmental regulation of mitochondrial activity. This requires regulation of the nuclear genome and the kinetoplast, the trypanosome's unusual mitochondrial genome. To investigate the potential cross talk between the nuclear and mitochondrial genome during the events of differentiation, we have 1) disrupted expression of a nuclear-encoded component of the cytochrome oxidase (COX) complex; and 2) generated dyskinetoplastid cells, which lack a mitochondrial genome. Using RNA interference (RNAi) and by disrupting the nuclear COX VI gene, we demonstrate independent regulation of COX component mRNAs encoded in the nucleus and kinetoplast. However, two independent approaches (acriflavine treatment and RNA interference ablation of mitochondrial topoisomerase II) failed to establish clonal lines of dyskinetoplastid bloodstream forms. Nevertheless, dyskinetoplastid forms generated in vivo could undergo two life cycle differentiation events: transition from bloodstream slender to stumpy forms and the initiation of transformation to procyclic forms. However, they subsequently arrested at a specific point in this developmental program before cell cycle reentry. These results provide strong evidence for a requirement for kinetoplast DNA in the bloodstream and for a kinetoplast-dependent control point during differentiation to procyclic forms.

Acriflavine↗

Beta1 integrin mediation of myogenic differentiation: implications for satellite cell differentiation.

Myoblast-extracellular matrix interactions mediated by integrin receptors have been shown to play a pivotal role in skeletal muscle development. In the current study, the avian genetic muscle weakness, low score normal (LSN), which exhibits modified myotube and sarcomere structure and a reduction in beta1 integrin expression during satellite cell differentiation, was used as a model system to further investigate the role of beta1 integrins in myogenic differentiation. During normal satellite cell differentiation, the beta1 integrin was localized at areas of pseudopodial activity and points of cell contact. In contrast, in LSN satellite cell cultures the beta1 integrin was predominantly observed in clusters not associated with points of cell to cell contact. The LSN satellite cells underwent apoptosis at the same time normal satellite cells were fusing to form multinucleated myotubes. During muscle development, the beta1 integrin is regulated by alternative splicing from a beta1A to beta1D form. During both embryonic and posthatch pectoralis major muscle development, regulation of the beta1A and beta1D variants was altered in the LSN. Normal and LSN myogenic satellite cell cultures did not express the beta1D integrin, but the LSN satellite cells expressed higher concentrations of the beta1A integrin than did normal satellite cells. Taken together, these data further demonstrate the importance of the beta1 integrin subunit in the regulation of cell-extracellular matrix signal transduction pathways during muscle growth and differentiation.

Amino Acid Sequence↗

Identification of a stress-induced protein during human trophoblast differentiation by differential display analysis.

Differentiation of human placental trophoblast is characterized by a process during which mononuclear villous cytotrophoblasts fuse to form a multinucleate syncytium. This event is associated with dramatic changes in gene expression. In the present study, we have applied a sensitive approach-differential display analysis-to evaluate changes in gene expression during in vitro forskolin-induced differentiation of a model of human trophoblast, the choriocarcinoma BeWo. We identified seven genes that were up-regulated; their expression and function have not previously been reported in trophoblast. Four up-regulated genes were novel upon comparison of their sequences to the GenBank database. The other three genes encode human cytochrome p450 IIC, inosine monophosphate dehydrogenase type II, and reducing agent and tunicamycin-responsive protein (RTP). Northern blot analysis revealed that RTP mRNA expression was induced to 3-fold in BeWo after 24-h incubation with forskolin and increased up to 11-fold by 72 h of forskolin treatment. The expression pattern of RTP was further investigated by in situ hybridization on second trimester and term placenta tissues. RTP mRNA was predominantly expressed in syncytiotrophoblasts in both second trimester and term placentae. The expression of RTP gene in BeWo cells was protein kinase C dependent. This is the first description of RTP gene expression in placenta and the first study elucidating the signaling pathway involved in the regulation of RTP gene expression. These results suggest that RTP may play a role in trophoblast cell proliferation and differentiation.

Blotting, Northern↗

Carcinoma showing thymus-like differentiation of the thyroid (CASTLE): a comparative study: evidence of thymic differentiation and solid cell nest origin.

Carcinoma showing thymus-like differentiation (CASTLE) is a rare intrathyroidal neoplasm, a member of a tumor family probably arising from ectopic thymus or branchial pouch remnants. Thyroid solid cell nests (SCNs) may also be derived from branchial pouch remnants. SCNs express p63, carcinoembryonic antigen (CEA), and high molecular weight keratin (HMWK). To determine whether CASTLE and SCNs derive from similar embryologic origins/lines of differentiation, and to better differentiate CASTLE from other thyroid neoplasms, we compared p63, CD5, HMWK, and CEA staining of CASTLE and SCNs with other thyroid and thymic lesions. Seven CASTLE, 11 SCNs, 10 thymic carcinoma, 11 invasive thymoma, 12 thymoma, 28 papillary thyroid carcinoma, 4 thyroid squamous cell carcinoma, 2 childhood sclerosing carcinoma, 4 follicular adenoma, 6 follicular carcinoma, 4 poorly differentiated carcinoma, and 20 lymphocytic thyroiditis cases were analyzed. In normal thyroid, only SCNs stained for p63, HMWK, and CEA. The only CD5-positive cells in normal thyroid were T cells. Thymomas and normal thymus stained similarly to SCNs. All CASTLE and thymic carcinomas exhibited diffuse p63 and HMWK staining and all CASTLE cases and the majority of thymic carcinomas were positive for CEA and CD5. In contrast, none of the other thyroid neoplasms examined exhibited consistent staining for all 4 markers studied. These findings provide further evidence that CASTLE is distinct from other thyroid neoplasms, is probably of thymic origin, and may arise from branchial pouch remnants, the thyroid SCNs. Moreover CD5, HMWK, CEA and p63 can be used to help distinguish CASTLE from other thyroid neoplasms.

Adult↗

Differential expression of the PTEN tumor suppressor protein in fetal and adult neuroendocrine tissues and tumors: progressive loss of PTEN expression in poorly differentiated neuroendocrine neoplasms.

Genetic alteration and loss of expression of tumor suppressor gene PTEN has been found in carcinomas of the breast, prostate, and endometrium, as well as in gliomas. PTEN expression in neural crest/neuroendocrine (NC/NE) tissues and in neoplasms has not been reported. This study examines PTEN expression in embryonal, fetal, and adult tissues by immunohistochemistry. The authors found high PTEN expression in embryonal, fetal, and adult NC/NE tissues. The authors also study the PTEN expression in NC/NE neoplasms (N = 37), including 5 melanocytic nevi, 2 melanomas, 9 carcinoids, 2 moderately differentiated neuroendocrine carcinomas, 13 poorly differentiated neuroendocrine carcinomas, 2 paragangliomas, 2 pheochromocytomas, 2 medullary thyroid carcinomas, and 1 neuroblastoma. All carcinoid tumors and melanocytic nevi showed moderate or strong immunostaining for PTEN. In contrast, the majority of poorly differentiated neuroendocrine carcinomas (7 of 13) were negative for PTEN (54%); the remainder showed diminished reactivity. The two melanomas studied were also negative for PTEN immunostaining. The paragangliomas, pheochromocytomas, medullary thyroid carcinomas, and neuroblastoma all showed a strong PTEN stain. The authors postulate that PTEN is a differentiation marker for NC/NE tissue and tumors and that loss of PTEN expression may represent an important step in the progression of NE tumors.

Adult↗

Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation.

Pdx1 (IPF-1 in humans, which is altered in MODY-4) is essential for pancreas development and mature beta-cell function. Pdx1 is expressed dynamically within the developing foregut, but how its expression characteristics are linked to the various steps of organ specification, differentiation, and function is unknown. Deletion of a conserved enhancer region (Area I-II-III) from Pdx1 produced a hypomorphic allele (Pdx1(DeltaI-II-III)) with altered timing and level of expression, which was studied in combination with wild-type and protein-null alleles. Lineage labeling in homozygous Area I-II-III deletion mutants (Pdx1(DeltaI-II-III/DeltaI-II-III)) revealed lack of ventral pancreatic bud specification and early-onset hypoplasia in the dorsal bud. Acinar tissue formed in the hypoplastic dorsal bud, but endocrine maturation was greatly impaired. While Pdx1(-/-) (protein-null) mice have nonpancreatic abnormalities (e.g., distorted pylorus, absent Brunner's glands), these structures formed normally in Pdx1(DeltaI-II-III/DeltaI-II-III) and Pdx1(DeltaI-II-III/-) mice. Surprisingly, heterozygous (Pdx1(+/DeltaI-II-III)) mice had abnormal islets and a more severe prediabetic condition than Pdx1(+/-) mice. These findings provide in vivo evidence of the differential requirements for the level of Pdx1 gene activity in the specification and differentiation of the various organs of the posterior foregut, as well as in pancreas and gut endocrine cell differentiation.

Animals↗

Differential expression of human cornifin alpha and beta in squamous differentiating epithelial tissues and several skin lesions.

Cornifins/small proline-rich proteins (SPRRs) belong to a family of proline-rich proteins that function as cornified envelope precursors. We report here an immunohistochemical analysis of human cornifin-alpha and -beta expression in several stratified squamous epithelia. In normal human skin, cornifin-alpha was expressed in the granular layer of the epidermis of palmoplantar skin, in the inner lining cells of the follicular infundibulum, and in the inner root sheath of the hair follicle. It was also expressed in the upper squamous layers of the oral, esophageal, and vaginal epithelia. Cornifin-beta was detected in oral, esophageal, and vaginal epithelia, but not in normal skin. Immunoblot analysis revealed quantitative differences in cornifin-alpha expression in skin from different regions. Studies of specimens from various skin diseases showed that (i) cornifin-alpha was upregulated in inflammatory skin diseases, hyperplastic lesions, and in well-differentiated squamous cell carcinomas (SCCs), (ii) the expression of cornifin-beta was absent in inflammatory skin but was detected in highly differentiated keratinocytes in well-differentiated SCCs of the skin and some other hyperproliferative skin lesions, and in SCCs of the oral mucosa and esophagus. Northern blot analysis revealed that cornifin-alpha mRNA was present in all the squamous epithelial tissues studied, whereas cornifin-beta mRNA was expressed in oral mucosal epithelia and verrucous carcinoma of the skin but neither in normal nor in psoriatic skin. These results indicate that (i) the amount of cornifin alpha/SPRR1 expression in normal human skin depends on the body region, (ii) cornifin-alpha/SPRR1, but not cornifin-beta, contributes to the integrity of the hair follicle, and (iii) the expression of cornifin-beta is induced in some hyperplastic skin diseases only when the keratinocytes undergo extensive squamous differentiation.

Blotting, Northern↗

Abnormal sequence of expression of differentiation markers in psoriatic epidermis: inversion of two steps in the differentiation program?

This immunohistologic study was undertaken to compare epidermal differentiation in normal and psoriatic skin. Although basal cells retain a normal phenotype in this disease, suprabasal layers exhibit abnormal sets of differentiation markers. The 67-kD keratin and Bd5 antigen, which are found in normal epidermis immediately above the basal layer, appear several layers higher in involved psoriatic epidermis. On the contrary, KF2 antigen, which is found in the upper spinous layers of normal epidermis, appears more precociously in psoriatic epidermis. Paradoxically, in this disease characterized by the absence of a granular layer, some markers specific for this layer in normal skin, such as involucrin and transglutaminase, appear in lower skin cell layers, while other granular markers, such as filaggrin, are either absent or found in the parakeratotic scales. These results point out the existence in psoriasis of a suprabasal cell population characterized by a set of markers that are never coexpressed in normal epidermis. The existence of this abnormal population of cells can be explained as the result of the inversion of two steps in the differentiation program. Thus, instead of an inability to express a given differentiation marker, psoriasis seems to be characterized by an abnormal sequence of expression of these markers.

Adult↗

Neural crest cell differentiation and carcinogenesis: capability of goldfish erythrophoroma cells for multiple differentiation and clonal polymorphism in their melanogenic variants.

Multiple differentiation shown by a single cell line (GEM 81) of goldfish erythrophoroma (tumors of integumental erythrophores) cells after administration of chemical induction in vitro includes 1) melanogenesis, 2) formation of reflecting platelets, 3) synthesis of pteridines heterogeneous to this species, 4) formation of dermal skeletons such as teeth and fin rays, 5) production of neuronal characters, and 6) genesis of lentoid bodies. Melanogenic cells, highest in inducibility, also show remarkable phenotypic diversification in their cell morphology, pigmentation, and physiologic response. In this paper, the following findings are presented; a) multiple differentiation shown by erythrophoroma cells occurs on a clonal basis, making whole component cells of a given induced colony strikingly similar in their cell characters, and b) induced melanogenic clones manifest a remarkable polymorphism in their melanosome ultrastructure and receptor composition associated with motile response. The divergence covers concentric lamellar, multivesicular, fibrillar, and macroglobular types for the former, and a varying combination of receptors for epinephrine, melanin concentrating hormone (MCH), and melatonin for the latter. Because a spectrum of phenotypes expressed by differentiation-induced erythrophoroma cells is restricted to those of neural crest origin (except lentoid bodies) and polymorphism in induced melanized cells is composed mostly of a collection of a variety of known melanogenic characters, it is presumed that erythrophoroma cells are capable of multiple differentiation within the commitment as neural crest cells.

Animals↗